Substituted benzimidazolone compounds

ABSTRACT

Disclosed are compounds of Formula (I) N-oxides, or salts thereof, wherein G, A, R1, and n are defined herein. Also disclosed are methods of using such compounds as inhibitors of signaling through Toll-like receptor 7, or 8, or 9, and pharmaceutical compositions comprising such compounds. These compounds are useful in treating inflammatory and autoimmune diseases.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of U.S. Provisional Application No.62/845,339, filed May 9, 2019, the contents of which are specificallyincorporated by reference herein.

DESCRIPTION

The present invention generally relates to substituted benzimidazolonecompounds useful as inhibitors of signaling through Toll-like receptor7, 8, or 9 (TLR7, TLR8, TLR9) or combinations thereof. Provided hereinare substituted benzimidazolone compounds, compositions comprising suchcompounds, and methods of their use. The invention further pertains topharmaceutical compositions containing at least one compound accordingto the invention that are useful for the treatment of conditions relatedto TLR modulation, such as inflammatory and autoimmune diseases, andmethods of inhibiting the activity of TLRs in a mammal.

Toll/IL-1 receptor family members are important regulators ofinflammation and host resistance. The Toll-like receptor familyrecognizes molecular patterns derived from infectious organismsincluding bacteria, fungi, parasites, and viruses (reviewed in Kawai, T.et al., Nature Immunol., 11:373-384 (2010)). Ligand binding to thereceptor induces dimerization and recruitment of adaptor molecules to aconserved cytoplasmic motif in the receptor termed the Toll/IL-1receptor (TIR) domain with the exception of TLR3, all TLRs recruit theadaptor molecule MyD88. The IL-1 receptor family also contains acytoplasmic TIR motif and recruits MyD88 upon ligand binding (reviewedin Sims, J. E. et al., Nature Rev. Immunol., 10:89-102 (2010)).

Toll-like receptors (TLRs) are a family of evolutionarily conserved,transmembrane innate immune receptors that participate in the first-linedefense. As pattern recognition receptors, the TLRs protect againstforeign molecules, activated by pathogen associated molecular patterns(PAMPs), or from damaged tissue, activated by danger associatedmolecular patterns (DAMPs). A total of 13 TLR family members have beenidentified, 10 in human, that span either the cell surface or theendosomal compartment. TLR7/8/9 are among the set that are endosomallylocated and respond to single-stranded RNA (TLR7 and TLR8) orunmethylated single-stranded DNA containing cytosine-phosphate-guanine(CpG) motifs (TLR9).

Activation of TLR7/8/9 can initiate a variety of inflammatory responses(cytokine production, B cell activation and IgG production, Type Iinterferon response). In the case of autoimmune disorders, the aberrantsustained activation of TLR7/8/9 leads to worsening of disease states.Whereas overexpression of TLR7 in mice has been shown to exacerbateautoimmune disease, knockout of TLR7 in mice was found to be protectiveagainst disease in lupus-prone MRL/lpr mice. Dual knockout of TLR7 and 9showed further enhanced protection.

As numerous conditions may benefit by treatment involving modulation ofcytokines, IFN production and B cell activity, it is immediatelyapparent that new compounds capable of modulating TLR7 and/or TLR8and/or TLR9 and methods of using these compounds could providesubstantial therapeutic benefits to a wide variety of patients.

SUMMARY OF THE INVENTION

The present invention relates to a new class of substitutedbenzimidazolone compounds found to be effective inhibitors of signalingthrough TLR7/8/9. These compounds are provided to be useful aspharmaceuticals with desirable stability, bioavailability, therapeuticindex, and toxicity values that are important to their drugability.

The present invention provides compounds of Formula (I) that are usefulas inhibitors of signaling through Toll-like receptor 7, 8, or 9 and areuseful for the treatment of proliferative diseases, allergic diseases,autoimmune diseases and inflammatory diseases, or stereoisomers,N-oxides, tautomers, pharmaceutically acceptable salts, solvates orprodrugs thereof.

The present invention also provides pharmaceutical compositionscomprising a pharmaceutically acceptable carrier and at least one of thecompounds of the present invention or stereoisomers, tautomers,pharmaceutically acceptable salts, solvates, or prodrugs thereof.

The present invention also provides a method for inhibition of Toll-likereceptor 7, 8, or 9 comprising administering to a host in need of suchtreatment a therapeutically effective amount of at least one of thecompounds of the present invention or stereoisomers, tautomers,pharmaceutically acceptable salts, solvates, or prodrugs thereof.

The present invention also provides a method for treating proliferative,metabolic, allergic, autoimmune and inflammatory diseases, comprisingadministering to a host in need of such treatment a therapeuticallyeffective amount of at least one of the compounds of the presentinvention or stereoisomers, tautomers, pharmaceutically acceptablesalts, solvates, or prodrugs thereof.

The present invention also provides a method of treating a disease ordisorder associated with Toll-like receptor 7, 8, or 9 activity, themethod comprising administering to a mammal in need thereof, at leastone of the compounds of Formula (I) or salts, solvates, and prodrugsthereof.

The present invention also provides processes and intermediates formaking the compounds of Formula (I) including salts, solvates, andprodrugs thereof.

The present invention also provides at least one of the compounds ofFormula (I) or salts, solvates, and prodrugs thereof, for use intherapy.

The present invention also provides the use of at least one of thecompounds of Formula (I) or salts, solvates, and prodrugs thereof, forthe manufacture of a medicament for the treatment of prophylaxis ofToll-like receptor 7, 8, or 9 related conditions, such as allergicdisease, autoimmune diseases, inflammatory diseases, and proliferativediseases.

The compound of Formula (I) and compositions comprising the compounds ofFormula (I) may be used in treating, preventing, or curing variousToll-like receptor 7, 8, or 9 related conditions. Pharmaceuticalcompositions comprising these compounds are useful for treating,preventing, or slowing the progression of diseases or disorders in avariety of therapeutic areas, such as allergic disease, autoimmunediseases, inflammatory diseases, and proliferative diseases.

These and other features of the invention will be set forth in expandedform as the disclosure continues.

DETAILED DESCRIPTION

The first aspect of the present invention provides at least one compoundof Formula (I):

-   or a salt thereof, wherein:-   G is:

-   (iv) a 9-membered heterocyclic ring selected from:

or

-   (v) 10-membered heterocyclic ring selected from:

-   each R₁ is independently hydrogen, F, Cl, —CN, C₁₋₃ alkyl, C₁₋₂    fluoroalkyl, —OCH₃, or —S(O)₂(C₁₋₃ alkyl);-   each R₂ is independently halo, —CN, —OH, —NO₂, C₁₋₄ alkyl, C₁₋₂    fluoroalkyl, C₁₋₂ cyanoalkyl, C₁₋₃ hydroxyalkyl, C₁₋₃ aminoalkyl,    —O(CH₂)₁₋₂OH, —(CH₂)₀₋₄O(C₁₋₄ alkyl), C₁₋₃ fluoroalkoxy,    —O(CH₂)₁₋₂OC(O)(C₁₋₃ alkyl), —O(CH₂)₁₋₂NR_(x)R_(x), —C(O)O(C₁₋₃    alkyl), —(CH₂)₀₋₂C(O)NR_(y)R_(y), —C(O)NR₄C₁₋₅ hydroxyalkyl),    —C(O)NR_(x)(C₂₋₆ alkoxyalkyl), —C(O)NR_(x)(C₃₋₆ cycloalkyl),    —NR_(y)R_(y), —NR_(y)(C₁₋₃ fluoroalkyl), —NR_(y)(C₁₋₄ hydroxyalkyl),    —NR_(x)CH₂(phenyl), —NR_(x)S(O)₂(C₃₋₆ cycloalkyl), —NR_(x)C(O)(C₁₋₃    alkyl), —NR_(x)CH₂(C₃₋₆ cycloalkyl), —(CH₂)₀₋₂S(O)₂(C₁₋₃ alkyl),    —(CH₂)₀₋₂(C₃₋₆ cycloalkyl), —(CH₂)₀₋₂(phenyl), morpholinyl,    dioxothiomorpholinyl, dimethyl pyrazolyl, methylpiperidinyl,    methylpiperazinyl, amino-oxadiazolyl, imidazolyl, pyrimidinyl,    triazolyl, or —C(O)(thiazolyl);-   R_(2a) is C₁₋₆ alkyl, C₁₋₃ fluoroalkyl, C₁₋₆ hydroxyalkyl, C₁₋₃    aminoalkyl, —(CH₂)₀₋₄O(C₁₋₃ alkyl), C₃₋₆ cycloalkyl,    —(CH₂)₁₋₃C(O)NR_(y)R_(y), —CH₂(C₃₋₆ cycloalkyl), —CH₂(phenyl),    tetrahydrofuranyl, tetrahydropyranyl, or phenyl;-   each R_(2b) is independently hydrogen, halo, —CN, —NR_(x)R_(x), C₁₋₆    alkyl, C₁₋₃ fluoroalkyl, C₁₋₃ hydroxyalkyl, C₁₋₃ fluoroalkoxy,    —(CH₂)₀₋₂O(C₁₋₃ alkyl), —(CH₂)₀₋₃C(O)NR_(x)R_(x), —(CH₂)₁₋₃(C₃₋₆    cycloalkyl), —C(O)O(C₁₋₃ alkyl), —C(O)NR_(x)(C₁₋₃ alkyl),    —CR_(x)═CR_(x)R_(x), or —CR_(x)═CH(C₃₋₆ cycloalkyl);-   R_(2c) is R_(2a) or R_(2b);-   R_(2d) is R_(2a) or R_(2b); provided that one of R_(2c) and R_(2d)    is R_(2a), and the other of R_(2c) and R₂ is R_(2b);-   A is —CR_(x)R_(x)R₃, —(CH₂)₁₋₂NR_(x)R₃, or R₃;-   R₃ is C₃₋₆ cycloalkyl, azetidinyl, morpholinyl, piperazinyl,    piperidinyl, or pyrrolidinyl, each substituted with zero to 2    R_(3a);-   each R_(3a) is independently C₁₋₆ alkyl, C₁₋₆ cyanoalkyl, C₁₋₆    fluoroalkyl, C₁₋₆ hydroxyalkyl, C₂₋₆ alkoxyalkyl,    —CH₂C(O)NR_(y)R_(y), —C(O)(CH₂)₁₋₃NR_(y)R_(y), —NR_(y)R_(y),    —NR_(y)(C₁₋₃ fluoroalkyl), —NR_(y)(C₂₋₄ alkoxyalkyl),    —(CH₂)₁₋₃S(O)₂(C₁₋₃ alkyl), —(CH₂)₁₋₃NR_(x)S(O)₂(C₁₋₃ alkyl),    —NR_(x)(CH₂)₁₋₂C(O)NR_(y)R_(y), —NR_(x)(CH₂)₁₋₃S(O)₂(C₁₋₃ alkyl),    —NR_(x)R_(w), —NR_(x)CH₂R_(w), R_(w), —CH₂R_(w),    oxaazaspiro[3.3]heptanyl, dioxothiaazaspiro[3.3]heptanyl,    oxaazabicyclo[3.2.1]octanyl, oxaazaspiro[3.4]octanyl, or    oxaazaspiro[3.5]nonanyl;-   R_(w) is C₃₋₆ cycloalkyl, azetidinyl, pyrrolidinyl, oxetanyl,    tetrahydrofuranyl, tetrahydropyranyl, piperidinyl, morpholinyl,    piperazinonyl, oxazepanyl, thiomorpholinyl, pyridinyl, pyrimidinyl,    or triazolyl, each substituted with zero to 3 substituents selected    from F, Cl, —OH, —CN, C₁₋₃ alkyl, C₁₋₃ hydroxyalkyl, C₁₋₃    fluoroalkyl, C₁₋₃ alkoxy —CH₂OCH₃, and —S(O)₂CH₃;-   each R_(x) is independently hydrogen or —CH₃;-   each R_(y) is independently hydrogen or C₁₋₆ alkyl;-   n is zero, 1, or 2; and-   p is zero, 1, or 2.

One embodiment provides a compound of Formula (I) or a salt thereofwherein:

-   G is:

and A, R₁, R₂. R_(2a), R_(2b), R_(2c), R_(2d), n, and p are defined inthe first aspect.

One embodiment provides a compound of Formula (I) or a salt thereofwherein:

-   G is a 9-membered heterocyclic ring selected from:

and A, R₁, R₂, n, and p are defined in the first aspect.

One embodiment provides a compound of Formula (I) or a salt thereofwherein:

-   G is a 10-membered heterocyclic ring selected from:

and A, R₁, R₂, n, and p are defined in the first aspect.

One embodiment provides a compound of Formula (I) or a salt thereofwherein: G is a 9-membered heterocyclic ring selected from:

and A, R₁, R₂, n, and p are defined in the first aspect.

One embodiment provides a compound of Formula (I) or a salt thereofhaving the structure for Formula (II):

wherein A, R₁, R₂, R_(3a), n, and p are defined in the first aspect.Included in this embodiment are compounds in which A is cyclohexyl orpiperidinyl, each substituted with zero to 2 R_(3a).

One embodiment provides a compound of Formula (I) or a salt thereofhaving the structure for Formula (III):

wherein A, R₁, R₂, R_(3a), n, and p are defined in the first aspect.Included in this embodiment are compounds in which A is cyclohexyl orpiperidinyl, each substituted with zero to 2 R_(3a).

One embodiment provides a compound of Formula (II) or a salt thereofwherein each R₁ is independently hydrogen, C₁₋₃ alkyl, or —CF₃; each R₂is independently hydrogen, —CH₃, or —OCH₃; A is cyclohexyl orpiperidinyl, each substituted with zero to 2 R_(3a); each R_(3a) isindependently C₁₋₆ alkyl, C₁₋₂ cyanoalkyl, C₁₋₄ fluoroalkyl, C₂₋₄alkoxyalkyl, —(CH₂)₁₋₃S(O)₂(C₁₋₃ alkyl), —CH₂(C₃₋₆ cycloalkyl),—CH₂R_(w), —CH₂C(O)NR_(x)R_(x), —NR_(y)R_(y), —NR_(x)(C₁₋₃ fluoroalkyl),—NR_(x)(C₂₋₄ alkoxyalkyl), —NR_(x)R_(w), —NR_(x)CH₂R_(w), R_(w),oxaazaspiro[3.3]heptanyl, dioxothiaazaspiro[3.3]heptanyl,oxaazabicyclo[3.2.1]octanyl, or oxaazaspiro[3.5]nonanyl; R_(w) is C₃₋₆cycloalkyl, azetidinyl, pyrrolidinyl, oxetanyl, tetrahydrofuranyl,tetrahydropyranyl, piperidinyl, piperazinonyl, oxazepanyl,thiomorpholinyl, pyridinyl, pyrimidinyl, or triazolyl, each substitutedwith zero to 2 substituents selected from F, —OH, C₁₋₃ alkyl, —CF₃,—OCH₃, —CH₂OCH₃, and —S(O)₂CH₃; each R_(x) is independently hydrogen or—CH₃; each R_(y) is independently hydrogen or C₁₋₆ alkyl; n is zero, 1,or 2; and p is zero, 1, or 2.

One embodiment provides a compound of Formula (I), N-oxide, or a saltthereof wherein each R₁ is independently hydrogen, F, Cl, —CN, C₁₋₃alkyl, C₁₋₂ fluoroalkyl, or —OCH₃; and A, R₂, n, and p are defined inthe first aspect. Included in this embodiment are compounds in whicheach R₁ is independently hydrogen, C₁₋₃ alkyl, or —CF₃. Also included inthis embodiment are compounds in which each R₁ is hydrogen, —CH₃,—CH₂CH₃, or —CH(CH₃)₂.

One embodiment provides a compound of Formula (I), N-oxide, or a saltthereof wherein each R₂ is independently F, Cl, —CN, C₁₋₄ alkyl, C₁₋₂fluoroalkyl, C₁₋₂ cyanoalkyl, C₁₋₃ hydroxyalkyl, —O(CH₂)₁₋₂OH,—(CH₂)₀₋₄O(C₁₋₄ alkyl), C₁₋₃ fluoroalkoxy, —(CH₂)₀₋₂C(O)NR_(y)R_(y),—C(O)NR_(x)(C₃₋₆ cycloalkyl), —NR_(y)R_(y), —NR_(x)S(O)₂(C₃₋₆cycloalkyl), —NR_(x)C(O)(C₁₋₃ alkyl), —NR_(x)CH₂(C₃₋₆ cycloalkyl),—(CH₂)₀₋₂S(O)₂(C₁₋₃ alkyl), or —(CH₂)₀₋₂(C₃₋₆ cycloalkyl); and A, R₁,R_(x), R_(y), n, and p are defined in the first aspect. Included in thisembodiment are compounds in which each R₂ is independently hydrogen,C₁₋₂ alkyl, —CF₃, or —OCH₃. Also included in this embodiment arecompounds in which each R₂ is independently hydrogen, —CH₃, or —OCH₃.

One embodiment provides a compound of Formula (I), N-oxide, or a saltthereof wherein Rea is C₁₋₄ alkyl, C₁₋₂ fluoroalkyl, C₁₋₄ hydroxyalkyl,or —(CH₂)₀₋₄O(C₁₋₃ alkyl); each R_(2b) is independently hydrogen, F, Cl,—CN, —NR_(x)R_(x), C₁₋₄ alkyl, C₁₋₂ fluoroalkyl, C₁₋₃ hydroxyalkyl, or—(CH₂)₀₋₂O(C₁₋₂ alkyl); and A, R₁, R_(x), and n are defined in the firstaspect.

One embodiment provides a compound of Formula (I), N-oxide, or a saltthereof wherein A is —CR_(x)R_(x)R₃, —CH₂NR_(x)R₃, or R₃; and R₁, R₂,R₃, R_(x), n, and p are defined in the first aspect. Included in thisembodiment are compounds in which A is —CR_(x)R_(x)R₃, or R₃. Alsoincluded in this embodiment are compounds in which A is —CR_(x)R_(x)R₃,—(CH₂)₁₋₂NR_(x)R₃, or R₃.

One embodiment provides a compound of Formula (I), N-oxide, or a saltthereof wherein A is R₃; and R₁, R₂, R₃, R_(3a), n, and p are defined inthe first aspect. Included in this embodiment are compounds in which R₃is C₅₋₆ cycloalkyl, piperazinyl, piperidinyl, or pyrrolidinyl, eachsubstituted with zero to 2 R_(3a). Also included in this embodiment arecompounds in which A is cyclohexyl or piperidinyl, each substituted withzero to 2 R_(3a). One embodiment provides a compound of Formula (I),N-oxide, or a salt thereof wherein A is cyclohexyl or piperidinyl, eachsubstituted with zero to 2 R_(3a); and R₁, R₂, R_(3a), R_(x), R_(y), n,and p are defined in the first aspect. Included in this embodiment arecompounds in which each R_(3a) is independently C₁₋₆ alkyl, C₁₋₂cyanoalkyl, C₁₋₄ fluoroalkyl, C₂₋₄ alkoxyalkyl, —(CH₂)₁₋₃S(O)₂(C₁₋₃alkyl), —CH₂(C₃₋₆ cycloalkyl), —CH₂R_(w), —CH₂C(O)NR_(x)R_(x),—NR_(y)R_(y), —NR_(x)(C₁₋₃ fluoroalkyl), —NR_(x)(C₂₋₄ alkoxyalkyl),—NR_(x)R_(w), —NR_(x)CH₂R_(w), R_(w), oxaazaspiro[3.3]heptanyl,dioxothiaazaspiro[3.3]heptanyl, oxaazabicyclo[3.2.1]octanyl, oroxaazaspiro[3.5]nonanyl; and R_(w) is C₃₋₆ cycloalkyl, azetidinyl,pyrrolidinyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl,piperidinyl, piperazinonyl, oxazepanyl, thiomorpholinyl, pyridinyl,pyrimidinyl, or triazolyl, each substituted with zero to 2 substituentsselected from F, —OH, C₁₋₃ alkyl, —CF₃, —OCH₃, —CH₂OCH₃, and —S(O)₂CH₃.

One embodiment provides a compound of Formula (I), N-oxide, or a saltthereof wherein A is cyclohexyl or piperidinyl, each substituted withzero to 1 R_(3a); each R_(3a) is independently —CH₃, —CH₂CH₃,—CH₂CH₂CH₃, —CH(CH₃)₂, —CH₂CH(CH₃)₂, —CH₂C(CH₃)₃, —CH(CH₃)CH₂CH₃,—CH₂CH₂CH(CH₃)₂, —CH(CH₂CH₃)₂, —CH₂CH(CH₂CH₃)₂, —CH₂CH₂C(CH₃)₃, —CH₂CN,—CH₂CH₂CF₃, —CH₂CH₂CH₂CF₃, —CH₂CH₂OCH₃, —CH₂CH₂S(O)₂CH₃, —CH₂(C₃₋₅cycloalkyl), —CH₂(pyridinyl), —CH₂(methoxypyrimidinyl),—CH₂(tetrahydrofuranyl), —CH₂(tetrahydropyranyl), —CH₂(methyltriazolyl),—CH₂C(O)NH₂, —CH₂C(O)NH(CH₃), —C(O)CH₂N(CH₃)₂, —NH₂, —NH(CH₂CH₃),—NH(CH₂CH₂CH₃), —NH(CH(CH₃)₂), —NH(CH₂CH(CH₃)₂), —NH(CH(CH₃)CH₂CH₃),—NH(CH₂C(CH₃)₃), —NH(CH₂CH(CH₂CH₃)₂), —NH(CH₂CH₂CF₃), —NH(CH₂CH₂OCH₃),—N(CH₃)₂, —N(CH₃)(CH(CH₃)₂)), —N(CH₃)(CH₂CH₂CF₃), —N(CH₂CH₃)₂,—N(CH₂CH₂CH₃)₂, —N(CH₂CH(CH₃)₂)₂, —NH(C₃₋₆ cycloalkyl), —NH(oxetanyl),—NH(tetrahydropyranyl), —NH(isopropylpiperidinyl),—N(CH₃)(tetrahydropyranyl), —N(CH₃)(cyclohexyl), —NH(CH₂(cyclopropyl)),—NH(CH₂(cyclohexyl)), —NH(CH₂(methylsulfonylcyclopropyl)),—NH(CH₂(tetrahydropyranyl)), —NH(CH₂(methyltriazolyl)),fluoroazetidinyl, difluoroazetidinyl, methoxyazetidinyl,hydroxy,trifluoromethylazetidinyl, cyclobutyl, oxetanyl,tetrahydrofuranyl, pyrrolidinyl, difluoropyrrolidinyl,tetrahydropyranyl, thiomorpholinyl, fluoropiperidinyl,difluoropiperidinyl, methoxypiperidinyl, methoxymethylpiperidinyl,methyl sulfonylpiperidinyl, piperazinonyl, oxazepanyl,oxaazaspiro[3.3]heptanyl, dioxothiaazaspiro[3.3]heptanyl,oxaazabicyclo[3.2.1]octanyl, or oxaazaspiro[3.5]nonanyl; and R₁, R₂, n,and p are defined in the first aspect. Included in this embodiment arecompounds in which A is cyclohexyl substituted with zero to 1 R_(3a).Also, included in this embodiment are compounds in which A ispiperidinyl substituted with zero to 1 R_(3a).

One embodiment provides a compound of Formula (I), N-oxide, or a saltthereof wherein said compound is:5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1-(1-methylpiperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(1);1-(1-isopropylpiperidin-4-yl)-6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(2);6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-methylpiperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(3);5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-methylpiperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(4);1-(1-isopropylpiperidin-4-yl)-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(5);1-(1-ethylpiperidin-4-yl)-6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(6);6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-propylpiperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(7);1-(1-ethylpiperidin-4-yl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1,3-dihydro-2H-benzo[d]imidazol-2-one(9);1-(1-isopropylpiperidin-4-yl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1,3-dihydro-2H-benzo[d]imidazol-2-one(10);(S)-6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-methylpiperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(11);(S)-1-(1-ethylpiperidin-3-yl)-6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(12);(S)-1-(1-isopropylpiperidin-3-yl)-6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(13);(S)-6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-(oxetan-3-yl)piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(14);(R)-6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-methylpiperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(15);(R)-1-(1-ethylpiperidin-3-yl)-6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(16);(R)-1-(1-isopropylpiperidin-3-yl)-6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(17);(R)-6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-(oxetan-3-yl)piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(18);1-((1s,4s)-4-(dimethylamino)cyclohexyl)-6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(19);1-((1s,4s)-4-(diethylamino)cyclohexyl)-6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(20); 1-((1s,4s)-4-(ethylamino)cyclohexyl)-6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(21);1-((1s,4s)-4-(isopropylamino)cyclohexyl)-6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(22);1-((1r,4r)-4-(dimethylamino)cyclohexyl)-6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(23);1-((1r,4s)-4-(ethylamino)cyclohexyl)-6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(24);1-((1r,4s)-4-(isopropylamino)cyclohexyl)-6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(25);(R)-6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-neopentylpiperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(26);(R)-6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-(tetrahydro-2H-pyran-4-yl)piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(27);1-((3R)-1-(sec-butyl)piperidin-3-yl)-6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(28);(R)-6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-(3,3,3-trifluoropropyl)piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(29);6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-((1s,4s)-4-((tetrahydro-2H-pyran-4-yl)amino)cyclohexyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(30);6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-((1s,4s)-4-(3,3,3-trifluoropropyl)amino)cyclohexyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(31);6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-((1s,4s)-4-(neopentylamino)cyclohexyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(32);6-methyl-1-((1s,4s)-4-(((1-methyl-1H-1,2,4-triazol-3-yl)methyl)amino)cyclohexyl)-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(33);1-((1s,4s)-4-(sec-butylamino)cyclohexyl)-6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(34);(R)-6-methyl-1-(1-((1-methyl-1H-1,2,4-triazol-3-yl)methyl)piperidin-3-yl)-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(35);(S)-1-(1-((2-methoxypyrimidin-5-yl)methyl)piperidin-3-yl)-6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(36);(R)-1-(1-(cyclopropylmethyl)piperidin-3-yl)-6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(37);(R)-1-(1-isopentylpiperidin-3-yl)-6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(38);(R)-6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-(4,4,4-trifluorobutyl)piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (39);(R)-1-(1-isobutylpiperidin-3-yl)-6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(40);(R)-6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-((tetrahydro-2H-pyran-4-yl)methyl)piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(41);(R)-6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-propylpiperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(42);6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-((3R)-1-((tetrahydrofuran-3-yl)methyl)piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(43);(R)-1-(1-(3,3-dimethylbutyl)piperidin-3-yl)-6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(44);(R)-1-(1-(2-ethylbutyl)piperidin-3-yl)-6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(45);(R)-6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-(pyridin-3-ylmethyl)piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(46);(R)-1-(1-(cyclopentylmethyl)piperidin-3-yl)-6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(47);1-((1s,4s)-4-(dimethylamino)cyclohexyl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1,3-dihydro-2H-benzo[d]imidazol-2-one(48);5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1-((1s,4s)-4-((tetrahydro-2H-pyran-4-yl)amino)cyclohexyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(49);1-((1s,4s)-4-(isopropylamino)cyclohexyl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1,3-dihydro-2H-benzo[d]imidazol-2-one(50);(R)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1-(1-methylpiperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(51);(R)-1-(1-ethylpiperidin-3-yl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1,3-dihydro-2H-benzo[d]imidazol-2-one(52);(R)-1-(1-isopropylpiperidin-3-yl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1,3-dihydro-2H-benzo[d]imidazol-2-one(53);(R)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1-(1-propylpiperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(54);(R)-1-(1-(cyclopropylmethyl)piperidin-3-yl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1,3-dihydro-2H-benzo[d]imidazol-2-one(55);(R)-1-(1-isobutylpiperidin-3-yl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1,3-dihydro-2H-benzo[d]imidazol-2-one(56);(R)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1-(1-((tetrahydro-2H-pyran-4-yl)methyl)piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(57);1-((1s,4s)-4-(cyclobutylamino)cyclohexyl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1,3-dihydro-2H-benzo[d]imidazol-2-one(58);5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1-((1s,4s)-4-(oxetan-3-ylamino)cyclohexyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(59);1-((1s,4s)-4-((cyclopropylmethyl)amino)cyclohexyl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1,3-dihydro-2H-benzo[d]imidazol-2-one(60);1-((1s,4s)-4-(isobutylamino)cyclohexyl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1,3-dihydro-2H-benzo[d]imidazol-2-one(61); 1-((1s,4s)-4-(cyclohexylamino)cyclohexyl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1,3-dihydro-2H-benzo[d]imidazol-2-one(62);1-((1s,4s)-4-(ethylamino)cyclohexyl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1,3-dihydro-2H-benzo[d]imidazol-2-one(63);5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1-((1s,4s)-4-(propylamino)cyclohexyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (64);1-((1s,4s)-4-(cyclopentylamino)cyclohexyl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1,3-dihydro-2H-benzo[d]imidazol-2-one(65);1-((1s,4s)-4-((cyclohexylmethyl)amino)cyclohexyl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1,3-dihydro-2H-benzo[d]imidazol-2-one(66);(R)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1-(1-(pentan-3-yl)piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (67);(R)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1-(1-(3,3,3-trifluoropropyl)piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(68);(R)-1-(1-cyclobutylpiperidin-3-yl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1,3-dihydro-2H-benzo[d]imidazol-2-one(69);(R)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1-(1-(tetrahydro-2H-pyran-4-yl)piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(70);(R)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1-(1-neopentylpiperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(71);(R)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1-(1-(oxetan-3-yl)piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(72);(R)-1-(1-(2-ethylbutyl)piperidin-3-yl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1,3-dihydro-2H-benzo[d]imidazol-2-one(73);5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-methylpiperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(74); 1-(1-(2-ethylbutyl)piperidin-4-yl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(75);5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-propylpiperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(76);1-(1-isopropylpiperidin-4-yl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(77);5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-((tetrahydro-2H-pyran-4-yl)methyl)piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(78);1-(1-(cyclopropylmethyl)piperidin-4-yl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(79);5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-(oxetan-3-yl)piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(80);5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-(tetrahydrofuran-3-yl)piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(81);5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-((tetrahydrofuran-3-yl)methyl)piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(82);1-(1-cyclobutylpiperidin-4-yl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(83); 1-((1s,4s)-4-(isopropyl(methyl)amino)cyclohexyl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1,3-dihydro-2H-benzo[d]imidazol-2-one(84);5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1-((1s,4s)-4-(methyl(tetrahydro-2H-pyran-4-yl)amino)cyclohexyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(85);2-(4-(5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidin-1-yl)-N,N-dimethylacetamide(86);2-(4-(5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidin-1-yl)-N-methylacetamide(87);N-methyl-2-(4-(6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidin-1-yl)acetamide(88);N,N-dimethyl-2-(4-(6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidin-1-yl)acetamide (89);N,N-dimethyl-2-(4-(5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidin-1-yl)acetamide(90);N,N-dimethyl-2-(4-(6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidin-1-yl)acetamide(91);(S)-2-(3-(6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidin-1-yl)acetamide(92);(S)—N,N-dimethyl-2-(3-(6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidin-1-yl)acetamide(93);(R)-2-(3-(6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidin-1-yl)acetamide(94);(R)—N,N-dimethyl-2-(3-(6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidin-1-yl)acetamide (95);(R)-2-(3-(6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidin-1-yl)acetonitrile(96);(R)-1-(1-(2-methoxyethyl)piperidin-3-yl)-6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(97);(R)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-(2-methoxyethyl)piperidin-3-yl)-6-methyl-1,3-dihydro-2H-benzo[d]imidazol-2-one(98);(R)-2-(3-(5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidin-1-yl)-N,N-dimethylacetamide(99);1-(1-(2-(dimethylamino)acetyl)piperidin-4-yl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1H-benzo[d]imidazol-2(3H)-one(100);1-(1-(dimethylglycyl)piperidin-4-yl)-6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(101);1-(1-(dimethylglycyl)piperidin-4-yl)-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(102);(S)-1-(1-(dimethylglycyl)piperidin-3-yl)-6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(103);(R)-1-(1-(dimethylglycyl)piperidin-3-yl)-6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(104);1-(1-(dimethylglycyl)piperidin-3-yl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1,3-dihydro-2H-benzo[d]imidazol-2-one(105);7-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-methylpiperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(106);1-(1-isopropylpiperidin-4-yl)-7-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(107);1-(1-ethylpiperidin-4-yl)-7-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(108);N,N-dimethyl-2-(4-(7-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidin-1-yl)acetamide(109);(R)-1-(1-ethylpiperidin-3-yl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-(trifluoromethyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(110);(R)-1-(1-isopropylpiperidin-3-yl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-(trifluoromethyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(111);(R)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-((tetrahydro-2H-pyran-4-yl)methyl)piperidin-3-yl)-6-(trifluoromethyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(112);(R)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-(oxetan-3-yl)piperidin-3-yl)-6-(trifluoromethyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(113);(R)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-methylpiperidin-3-yl)-6-(trifluoromethyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(114);(R)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-propylpiperidin-3-yl)-6-(trifluoromethyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(115);(R)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-neopentylpiperidin-3-yl)-6-(trifluoromethyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(116);(R)-1-(1-(2-ethylbutyl)piperidin-3-yl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-(trifluoromethyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(117);(R)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-(2-methoxyethyl)piperidin-3-yl)-6-(trifluoromethyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(118);(S)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-methylpiperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(119);(S)-6-isopropyl-1-(1-isopropylpiperidin-3-yl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(120);(S)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-propylpiperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(121);(S)-1-(1-cyclobutylpiperidin-3-yl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(122);(S)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-(oxetan-3-yl)piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(123);(S)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-(tetrahydro-2H-pyran-4-yl)piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(124);(S)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-((tetrahydro-2H-pyran-4-yl)methyl)piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(125);6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-((3S)-1-((tetrahydrofuran-3-yl)methyl)piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(126);(S)-1-(1-(cyclopropylmethyl)piperidin-3-yl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(127);(S)-1-(1-(cyclopropylmethyl)piperidin-3-yl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(128);(S)-1-(1-isobutylpiperidin-3-yl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(129);(S)-1-(1-(2-ethylbutyl)piperidin-3-yl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(130);(S)-1-(1-isopentylpiperidin-3-yl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(131);(S)-1-(1-isopentylpiperidin-3-yl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(132);(S)-1-(1-(cyclobutylmethyl)piperidin-3-yl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(133);(R)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-propylpiperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(134);(R)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-(oxetan-3-yl)piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(135);(R)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-methylpiperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(136);(R)-6-isopropyl-1-(1-isopropylpiperidin-3-yl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(137);(R)-1-(1-ethylpiperidin-3-yl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(138);(R)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-((tetrahydro-2H-pyran-4-yl)methyl)piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(139);(R)-1-(1-(cyclobutylmethyl)piperidin-3-yl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(140);(R)-1-(1-isobutylpiperidin-3-yl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(141);(R)-1-(1-(cyclopropylmethyl)piperidin-3-yl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(142);(R)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-(tetrahydro-2H-pyran-4-yl)piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(143);(R)-1-(1-ethylpiperidin-3-yl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(144);(R)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-1-(1-isopropylpiperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(145);(R)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-1-(1-(oxetan-3-yl)piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(146);(R)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-1-(1-methylpiperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(147);(R)-1-(1-(2-ethylbutyl)piperidin-3-yl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(148);(R)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-1-(1-((tetrahydro-2H-pyran-4-yl)methyl)piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(149);(R)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-1-(1-propylpiperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(150);(R)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-(2-ethylbutyl)piperidin-3-yl)-6-isopropyl-1,3-dihydro-2H-benzo[d]imidazol-2-one (151);(R)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-1-(1-neopentylpiperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(152);(R)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-neopentylpiperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(153);6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-methylpiperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(154);6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-propylpiperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(155);1-(1-cyclobutylpiperidin-4-yl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(156);6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-(oxetan-3-yl)piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(157);6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-(tetrahydro-2H-pyran-4-yl)piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(158);6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-((tetrahydro-2H-pyran-4-yl)methyl)piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(159);6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-((tetrahydrofuran-3-yl)methyl)piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(160);1-(1-(cyclopropylmethyl)piperidin-4-yl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(161);6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-(tetrahydrofuran-3-yl)piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (162);6-isopropyl-1-(1-isopropylpiperidin-4-yl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(163);1-(1-isobutylpiperidin-4-yl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(164);1-(1-(2-ethylbutyl)piperidin-4-yl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(165);6-ethyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-((1s,4s)-4-((tetrahydro-2H-pyran-4-yl)amino)cyclohexyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(166);6-ethyl-1-((1s,4s)-4-(isopropylamino)cyclohexyl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(167);1-((1s,4s)-4-(dipropylamino)cyclohexyl)-6-ethyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(168);1-((1s,4s)-4-(diethylamino)cyclohexyl)-6-ethyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(169);6-ethyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-((1s,4s)-4-(oxetan-3-ylamino)cyclohexyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(170);(R)-6-ethyl-1-(1-ethylpiperidin-3-yl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(171);(R)-6-ethyl-1-(1-isopropylpiperidin-3-yl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(172);(R)-6-ethyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-(oxetan-3-yl)piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(173);(R)-6-ethyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-methylpiperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(174);(R)-6-ethyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-((tetrahydro-2H-pyran-4-yl)methyl)piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (175);1-((3R)-1-(sec-butyl)piperidin-3-yl)-6-ethyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(176);(R)-6-ethyl-1-(1-isobutylpiperidin-3-yl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(177);(R)-6-ethyl-1-(1-(2-ethylbutyl)piperidin-3-yl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(178);(R)-6-ethyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-propylpiperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(179);(R)-6-ethyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-neopentylpiperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(180);(R)-1-(1-(cyclobutylmethyl)piperidin-3-yl)-6-ethyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(181);(R)-1-(1-(cyclopropylmethyl)piperidin-3-yl)-6-ethyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(182);(R)-6-ethyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-(3,3,3-trifluoropropyl)piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(183);(R)-6-ethyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-(tetrahydro-2H-pyran-4-yl)piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(184);5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-((1s,4s)-4-(dimethylamino)cyclohexyl)-6-isopropyl-1,3-dihydro-2H-benzo[d]imidazol-2-one(185);5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-1-((1s,4s)-4-(isopropylamino)cyclohexyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(186);5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-1-((1s,4s)-4-((tetrahydro-2H-pyran-4-yl)amino)cyclohexyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(187);5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-1-((1s,4s)-4-(oxetan-3-ylamino)cyclohexyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(188);5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-((1s,4s)-4-(ethylamino)cyclohexyl)-6-isopropyl-1,3-dihydro-2H-benzo[d]imidazol-2-one(189);5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-1-((1s,4s)-4-(neopentylamino)cyclohexyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(190);1-((1s,4s)-4-(dimethylamino)cyclohexyl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(191); 6-isopropyl-1-((1s,4s)-4-(isopropylamino)cyclohexyl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(192);6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-((1s,4s)-4-((tetrahydro-2H-pyran-4-yl)amino)cyclohexyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(193);1-((1s,4s)-4-(2-ethylbutyl)amino)cyclohexyl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(194);6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-((1s,4s)-4-(propylamino)cyclohexyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(195);6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-((1s,4s)-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)cyclohexyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (196);6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-((1s,4s)-4-(neopentylamino)cyclohexyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(197);5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-((1s,4s)-4-(2-ethylbutyl)amino)cyclohexyl)-6-isopropyl-1,3-dihydro-2H-benzo[d]imidazol-2-one(198);5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-((1s,4s)-4-(dipropylamino)cyclohexyl)-6-isopropyl-1,3-dihydro-2H-benzo[d]imidazol-2-one(199);5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-1-((1s,4s)-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)cyclohexyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(200);6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-((1r,4r)-4-(oxetan-3-ylamino)cyclohexyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (201);1-((1r,4r)-4-(dimethylamino)cyclohexyl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(202);6-isopropyl-1-((1r,4s)-4-(isopropylamino)cyclohexyl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(203);1-((1r,4s)-4-(isobutylamino)cyclohexyl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(204); 1-((1r,4r)-4-(diisobutylamino)cyclohexyl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(205);1-((1r,4s)-4-(bis(cyclopropylmethyl)amino)cyclohexyl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(206); 6-isopropyl-1-((1r,4r)-4-((1-isopropylpiperidin-4-yl)amino)cyclohexyl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(207);(R)-1-(1-(3,3-dimethylbutyl)piperidin-3-yl)-6-ethyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(208);(R)-1-(1-(cyclopentylmethyl)piperidin-3-yl)-6-ethyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(209); (R)-1-(1-(3,3-dimethylbutyl)piperidin-3-yl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(210);(R)-1-(1-(cyclopentylmethyl)piperidin-3-yl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(211);6-ethyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-((3R)-1-(tetrahydrofuran-3-yl)piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(212);6-ethyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-((3R)-1-(tetrahydrofuran-3-yl)piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(213);6-ethyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-((3R)-1-(tetrahydro-2H-pyran-3-yl)piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(214-215);6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-((3R)-1-(tetrahydrofuran-3-yl)piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(216-217);6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-((3R)-1-(tetrahydro-2H-pyran-3-yl)piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(218-219);(S)-2-(3-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidin-1-yl)acetamide(220);(S)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-(2-methoxyethyl)piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(221);(S)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-(2-(methylsulfonyl)ethyl)piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(222);6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-(2-methoxyethyl)piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(223);6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-(2-(methylsulfonyl)ethyl)piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (224);(R)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-(2-methoxyethyl)piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(225);(R)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-(2-methoxyethyl)piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(226);(R)-6-ethyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-(2-methoxyethyl)piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(227);(R)-1-(1-(dimethylglycyl)piperidin-3-yl)-6-ethyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(228);1-(4-(4,4-difluoropiperidin-1-yl)cyclohexyl)-6-isopropyl-5-(8-methoxy-7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(229-230);6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(4-(pyrrolidin-1-yl)cyclohexyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(231);6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(4-(pyrrolidin-1-yl)cyclohexyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (232);6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(4-(3-oxopiperazin-1-yl)cyclohexyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(233-234);1-(4-(7-oxa-2-azaspiro[3.5]nonan-2-yl)cyclohexyl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(235-236);6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(4-(3-methoxyazetidin-1-yl)cyclohexyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(237-238);1-(4-(2-oxa-7-azaspiro[3.5]nonan-7-yl)cyclohexyl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(239-240);1-(4-(3-hydroxy-3-(trifluoromethyl)azetidin-1-yl)cyclohexyl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(241-242);6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(4-(3-oxopiperazin-1-yl)cyclohexyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (243);1-(4-(2,2-dioxido-2-thia-6-azaspiro[3.3]heptan-6-yl)cyclohexyl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(244-245);1-(4-(4,4-difluoropiperidin-1-yl)cyclohexyl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(246-247);6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(4-(methyl(3,3,3-trifluoropropyl)amino)cyclohexyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(248-249);6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(4-thiomorpholinocyclohexyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(250-251);1-(4-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)cyclohexyl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(252-253);1-(4-(2-oxa-6-azaspiro[3.3]heptan-6-yl)cyclohexyl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(254);6-isopropyl-5-(8-methoxy-7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(4-(2-methoxyethyl)amino)cyclohexyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(257-258);6-isopropyl-5-(8-methoxy-7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(4-((1-(methylsulfonyl)cyclopropyl)methyl)amino)cyclohexyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(259-260);1-(4-(1,4-oxazepan-4-yl)cyclohexyl)-6-isopropyl-5-(8-methoxy-7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(261-262);1-(4-(3-fluoroazetidin-1-yl)cyclohexyl)-6-isopropyl-5-(8-methoxy-7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(263-264);6-isopropyl-5-(8-methoxy-7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(4-(3-methoxyazetidin-1-yl)cyclohexyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(265-266);1-(4-(2-oxa-7-azaspiro[3.5]nonan-7-yl)cyclohexyl)-6-isopropyl-5-(8-methoxy-7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(267-268);1-(4-(2-oxa-6-azaspiro[3.3]heptan-6-yl)cyclohexyl)-6-isopropyl-5-(8-methoxy-7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(269-270);1-(4-(1,4-oxazepan-4-yl)cyclohexyl)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-1,3-dihydro-2H-benzo[d]imidazol-2-one(271-272);5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(4-(3-fluoropiperidin-1-yl)cyclohexyl)-6-isopropyl-1,3-dihydro-2H-benzo[d]imidazol-2-one(273-274); 1-(4-(4,4-difluoropiperidin-1-yl)cyclohexyl)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-1,3-dihydro-2H-benzo[d]imidazol-2-one(275-276);5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-1-(4-(3-methoxyazetidin-1-yl)cyclohexyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(277-278);5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(4-(3-fluoroazetidin-1-yl)cyclohexyl)-6-isopropyl-1,3-dihydro-2H-benzo[d]imidazol-2-one(279-280);1-(4-(2-oxa-6-azaspiro[3.3]heptan-6-yl)cyclohexyl)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-1,3-dihydro-2H-benzo[d]imidazol-2-one(281);1-(4-(2-oxa-7-azaspiro[3.5]nonan-7-yl)cyclohexyl)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-1,3-dihydro-2H-benzo[d]imidazol-2-one(282-283);6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(4-(3-methoxypyrrolidin-1-yl)cyclohexyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(284-285);(S)-1-(4-(3-fluoropyrrolidin-1-yl)cyclohexyl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(286-287);6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(4-(3-(methylsulfonyl)pyrrolidin-1-yl)cyclohexyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(288-289);(R)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(4-(3-(methoxymethyl)pyrrolidin-1-yl)cyclohexyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(290-291);1-(4-((3S,4R)-3,4-difluoropyrrolidin-1-yl)cyclohexyl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(292-293);1-(4-(3,3-difluoropyrrolidin-1-yl)cyclohexyl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(294-295);1-(4-(3,3-difluoroazetidin-1-yl)cyclohexyl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(296); 1-(4-(2-oxa-6-azaspiro[3.3]heptan-6-yl)cyclohexyl)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-1,3-dihydro-2H-benzo[d]imidazol-2-one(297);5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1-(piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(1E);6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(1EA);5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(1EB);6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(1EC);(R)-6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(1ED);1-((1r,4r)-4-aminocyclohexyl)-6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(1EF);1-((1s,4s)-4-aminocyclohexyl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1,3-dihydro-2H-benzo[d]imidazol-2-one(1EG);(R)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1-(piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(1EH);5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(1EG);7-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(106F);(S)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(110F);(R)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(119F);6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(119FA);(R)-6-ethyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(119FB); or(R)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-1-(piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(119FC).

The present invention may be embodied in other specific forms withoutdeparting from the spirit or essential attributes thereof. The inventionencompasses all combinations of the aspects and/or embodiments of theinvention noted herein. It is understood that any and all embodiments ofthe present invention may be taken in conjunction with any otherembodiment or embodiments to describe additional embodiments. It is alsoto be understood that each individual element of the embodiments ismeant to be combined with any and all other elements from any embodimentto describe an additional embodiment.

Definitions

The features and advantages of the invention may be more readilyunderstood by those of ordinary skill in the art upon reading thefollowing detailed description. It is to be appreciated that certainfeatures of the invention that are, for clarity reasons, described aboveand below in the context of separate embodiments, may also be combinedto form a single embodiment. Conversely, various features of theinvention that are, for brevity reasons, described in the context of asingle embodiment, may also be combined so as to form sub-combinationsthereof. Embodiments identified herein as exemplary or preferred areintended to be illustrative and not limiting.

Unless specifically stated otherwise herein, references made in thesingular may also include the plural. For example, “a” and “an” mayrefer to either one, or one or more.

As used herein, the phrase “compounds” refers to at least one compound.For example, a compound of Formula (I) includes a compound of Formula(I) and two or more compounds of Formula (I).

Unless otherwise indicated, any heteroatom with unsatisfied valences isassumed to have hydrogen atoms sufficient to satisfy the valences.

The definitions set forth herein take precedence over definitions setforth in any patent, patent application, and/or patent applicationpublication incorporated herein by reference.

Listed below are definitions of various terms used to describe thepresent invention. These definitions apply to the terms as they are usedthroughout the specification (unless they are otherwise limited inspecific instances) either individually or as part of a larger group.

Throughout the specification, groups and substituents thereof may bechosen by one skilled in the field to provide stable moieties andcompounds.

In accordance with a convention used in the art,

is used in structural formulas herein to depict the bond that is thepoint of attachment of the moiety or substituent to the core or backbonestructure.

The terms “halo” and “halogen,” as used herein, refer to F, Cl, Br, andI.

The term “cyano” refers to the group —CN.

The term “amino” refers to the group —NH₂.

The term “oxo” refers to the group ═O.

The term “alkyl” as used herein, refers to both branched andstraight-chain saturated aliphatic hydrocarbon groups containing, forexample, from 1 to 12 carbon atoms, from 1 to 6 carbon atoms, and from 1to 4 carbon atoms. Examples of alkyl groups include, but are not limitedto, methyl (Me), ethyl (Et), propyl (e.g., n-propyl and i-propyl), butyl(e.g., n-butyl, i-butyl, sec-butyl, and t-butyl), and pentyl (e.g.,n-pentyl, isopentyl, neopentyl), n-hexyl, 2-methylpentyl, 2-ethylbutyl,3-methylpentyl, and 4-methylpentyl. When numbers appear in a subscriptafter the symbol “C”, the subscript defines with more specificity thenumber of carbon atoms that a particular group may contain. For example,“C₁₋₆ alkyl” denotes straight and branched chain alkyl groups with oneto six carbon atoms.

The term “fluoroalkyl” as used herein is intended to include bothbranched and straight-chain saturated aliphatic hydrocarbon groupssubstituted with one or more fluorine atoms. For example, “C₁₋₄fluoroalkyl” is intended to include C₁, C₂, C₃, and C₄ alkyl groupssubstituted with one or more fluorine atoms. Representative examples offluoroalkyl groups include, but are not limited to, —CF₃ and —CH₂CF₃.

The term “cyanoalkyl” includes both branched and straight-chainsaturated alkyl groups substituted with one or more cyano groups. Forexample, “cyanoalkyl” includes —CH₂CN, —CH₂CH₂CN, and C₁₋₄ cyanoalkyl.

The term “aminoalkyl” includes both branched and straight-chainsaturated alkyl groups substituted with one or more amine groups. Forexample, “aminoalkyl” includes —CH₂NH₂, —CH₂CH₂NH₂, and C₁₋₄ aminoalkyl.

The term “hydroxyalkyl” includes both branched and straight-chainsaturated alkyl groups substituted with one or more hydroxyl groups. Forexample, “hydroxyalkyl” includes —CH₂OH, —CH₂CH₂OH, and C₁₋₄hydroxyalkyl.

The term “cycloalkyl,” as used herein, refers to a group derived from anon-aromatic monocyclic or polycyclic hydrocarbon molecule by removal ofone hydrogen atom from a saturated ring carbon atom. Representativeexamples of cycloalkyl groups include, but are not limited to,cyclopropyl, cyclopentyl, and cyclohexyl. When numbers appear in asubscript after the symbol “C”, the subscript defines with morespecificity the number of carbon atoms that a particular cycloalkylgroup may contain. For example, “C₃-C₆ cycloalkyl” denotes cycloalkylgroups with three to six carbon atoms.

The term “alkoxy,” as used herein, refers to an alkyl group attached tothe parent molecular moiety through an oxygen atom, for example, methoxygroup (—OCH₃). For example, “C₁₋₃ alkoxy” denotes alkoxy groups with oneto three carbon atoms.

The terms “fluoroalkoxy” and “—O(fluoroalkyl)” represent a fluoroalkylgroup as defined above attached through an oxygen linkage (—O—). Forexample, “C₁₋₄ fluoroalkoxy” is intended to include C₁, C₂, C₃, and C₄fluoroalkoxy groups. The term “alkoxyalkyl,” as used herein, refers toan alkoxy group attached through its oxygen atom to an alkyl group,which is attached to the parent molecular moiety, for example,methoxymethyl group (—CH₂OCH₃). For example, “C₂₋₄ alkoxyalkyl” denotesalkoxyalkyl groups with two to four carbon atoms, such as —CH₂OCH₃,—CH₂CH₂OCH₃, —CH₂OCH₂CH₃, and —CH₂CH₂OCH₂CH₃.

The phrase “pharmaceutically acceptable” is employed herein to refer tothose compounds, materials, compositions, and/or dosage forms which are,within the scope of sound medical judgment, suitable for use in contactwith the tissues of human beings and animals without excessive toxicity,irritation, allergic response, or other problem or complication,commensurate with a reasonable benefit/risk ratio.

The compounds of Formula (I) can form salts which are also within thescope of this invention. Unless otherwise indicated, reference to aninventive compound is understood to include reference to one or moresalts thereof. The term “salt(s)” denotes acidic and/or basic salt(s)formed with inorganic and/or organic acids and bases. In addition, theterm “salt(s) may include zwitterions (inner salts), e.g., when acompound of Formula (I) contains both a basic moiety, such as an amineor a pyridine or imidazole ring, and an acidic moiety, such as acarboxylic acid. Pharmaceutically acceptable (i.e., non-toxic,physiologically acceptable) salts are preferred, such as, for example,acceptable metal and amine salts in which the cation does not contributesignificantly to the toxicity or biological activity of the salt.However, other salts may be useful, e.g., in isolation or purificationsteps which may be employed during preparation, and thus, arecontemplated within the scope of the invention. Salts of the compoundsof the formula (I) may be formed, for example, by reacting a compound ofthe Formula (I) with an amount of acid or base, such as an equivalentamount, in a medium such as one in which the salt precipitates or in anaqueous medium followed by lyophilization.

Exemplary acid addition salts include acetates (such as those formedwith acetic acid or trihaloacetic acid, for example, trifluoroaceticacid), adipates, alginates, ascorbates, aspartates, benzoates,benzenesulfonates, bisulfates, borates, butyrates, citrates,camphorates, camphorsulfonates, cyclopentanepropionates, digluconates,dodecyl sulfates, ethanesulfonates, fumarates, glucoheptanoates,glycerophosphates, hemi sulfates, heptanoates, hexanoates,hydrochlorides (formed with hydrochloric acid), hydrobromides (formedwith hydrogen bromide), hydroiodides, maleates (formed with maleicacid), 2-hydroxyethanesulfonates, lactates, methanesulfonates (formedwith methanesulfonic acid), 2-naphthalenesulfonates, nicotinates,nitrates, oxalates, pectinates, persulfates, 3-phenylpropionates,phosphates, picrates, pivalates, propionates, salicylates, succinates,sulfates (such as those formed with sulfuric acid), sulfonates (such asthose mentioned herein), tartrates, thiocyanates, toluenesulfonates suchas tosylates, undecanoates, and the like.

Exemplary basic salts include ammonium salts, alkali metal salts such assodium, lithium, and potassium salts; alkaline earth metal salts such ascalcium and magnesium salts; barium, zinc, and aluminum salts; saltswith organic bases (for example, organic amines) such as trialkylaminessuch as triethylamine, procaine, dibenzylamine,N-benzyl-β-phenethylamine, 1-ephenamine, N,N′-dibenzylethylene-diamine,dehydroabietylamine, N-ethylpiperidine, benzylamine, dicyclohexylamineor similar pharmaceutically acceptable amines and salts with amino acidssuch as arginine, lysine and the like. Basic nitrogen-containing groupsmay be quaternized with agents such as lower alkyl halides (e.g.,methyl, ethyl, propyl, and butyl chlorides, bromides and iodides),dialkyl sulfates (e.g., dimethyl, diethyl, dibutyl, and diamylsulfates), long chain halides (e.g., decyl, lauryl, myristyl and stearylchlorides, bromides and iodides), aralkyl halides (e.g., benzyl andphenethyl bromides), and others. Preferred salts includemonohydrochloride, hydrogensulfate, methanesulfonate, phosphate ornitrate salts.

The compounds of Formula (I) can be provided as amorphous solids orcrystalline solids. Lyophilization can be employed to provide thecompounds of Formula (I) as amorphous solids.

It should further be understood that solvates (e.g., hydrates) of thecompounds of Formula (I) are also within the scope of the presentinvention. The term “solvate” means a physical association of a compoundof Formula (I) with one or more solvent molecules, whether organic orinorganic. This physical association includes hydrogen bonding. Incertain instances the solvate will be capable of isolation, for examplewhen one or more solvent molecules are incorporated in the crystallattice of the crystalline solid. “Solvate” encompasses bothsolution-phase and isolable solvates. Exemplary solvates includehydrates, ethanolates, methanolates, isopropanolates, acetonitrilesolvates, and ethyl acetate solvates. Methods of solvation are known inthe art.

Various forms of prodrugs are well known in the art and are describedin:

a) The Practice of Medicinal Chemistry, Camille G. Wermuth et al., Ch31, (Academic Press, 1996);

b) Design of Prodrugs, edited by H. Bundgaard, (Elsevier, 1985);

c) A Textbook of Drug Design and Development, P. Krogsgaard-Larson andH. Bundgaard, eds. Ch 5, pgs 113-191 (Harwood Academic Publishers,1991); and

d) Hydrolysis in Drug and Prodrug Metabolism, Bernard Testa and JoachimM. Mayer, (Wiley-VCH, 2003).

Preparation of prodrugs is well known in the art and described in, forexample, King, F. D., ed., Medicinal Chemistry: Principles and Practice,The Royal Society of Chemistry, Cambridge, UK (1994); Testa, B. et al.,Hydrolysis in Drug and Prodrug Metabolism. Chemistry, Biochemistry andEnzymology, VCHA and Wiley-VCH, Zurich, Switzerland (2003); Wermuth, C.G., ed., The Practice of Medicinal Chemistry, Academic Press, San Diego,Calif. (1999); Rautio, J. et al., Nature Review Drug Discovery, 17,559-587, (2018).

In addition, compounds of Formula (I), subsequent to their preparation,can be isolated and purified to obtain a composition containing anamount by weight equal to or greater than 99% of a compound of Formula(I) (“substantially pure”), which is then used or formulated asdescribed herein. Such “substantially pure” compounds of Formula (I) arealso contemplated herein as part of the present invention.

“Stable compound” and “stable structure” are meant to indicate acompound that is sufficiently robust to survive isolation to a usefuldegree of purity from a reaction mixture, and formulation into anefficacious therapeutic agent. The present invention is intended toembody stable compounds.

“Therapeutically effective amount” is intended to include an amount of acompound of the present invention alone or an amount of the combinationof compounds claimed or an amount of a compound of the present inventionin combination with other active ingredients effective to act as aninhibitor to TLR7/8/9, or effective to treat or prevent autoimmuneand/or inflammatory disease states, such as SLE, IBD, multiple sclerosis(MS), and Sjögren's syndrome, and rheumatoid arthritis.

As used herein, “treating” or “treatment” cover the treatment of adisease-state in a mammal, particularly in a human, and include: (a)preventing the disease-state from occurring in a mammal, in particular,when such mammal is predisposed to the disease-state but has not yetbeen diagnosed as having it; (b) inhibiting the disease-state, i.e.,arresting its development; and/or (c) relieving the disease-state, i.e.,causing regression of the disease state.

The compounds of the present invention are intended to include allisotopes of atoms occurring in the present compounds. Isotopes includethose atoms having the same atomic number but different mass numbers. Byway of general example and without limitation, isotopes of hydrogeninclude deuterium (D) and tritium (T). Isotopes of carbon include ¹³Cand ¹⁴C. Isotopically-labeled compounds of the invention can generallybe prepared by conventional techniques known to those skilled in the artor by processes analogous to those described herein, using anappropriate isotopically-labeled reagent in place of the non-labeledreagent otherwise employed. For example, methyl (—CH₃) also includesdeuterated methyl groups such as —CD₃.

Utility

The human immune system has evolved to defend the body frommicro-organisms, viruses, and parasites that can cause infection,disease or death. Complex regulatory mechanisms ensure that the variouscellular components of the immune system target the foreign substancesor organisms, while not causing permanent or significant damage to theindividual. While the initiating events are not well understood at thistime, in autoimmune disease states the immune system directs itsinflammatory response to target organs in the afflicted individual.Different autoimmune diseases are typically characterized by thepredominate or initial target organ or tissues affected; such as thejoint in the case of rheumatoid arthritis, the thyroid gland in the caseof Hashimoto's thyroiditis, the central nervous system in the case ofmultiple sclerosis, the pancreas in the case of type I diabetes, and thebowel in the case of inflammatory bowel disease.

The compounds of the invention inhibit signaling through Toll-likereceptor 7, or 8, or 9 (TLR7, TLR8, TLR9) or combinations thereof.Accordingly, compounds of Formula (I) have utility in treatingconditions associated with the inhibition of signaling through one ormore of TLR7, TLR8, or TLR9. Such conditions include TLR7, TLR8, or TLR9receptor associated diseases in which cytokine levels are modulated as aconsequence of intracellular signaling.

As used herein, the terms “treating” or “treatment” encompass thetreatment of a disease state in a mammal, particularly in a human, andinclude: (a) preventing or delaying the occurrence of the disease statein a mammal, in particular, when such mammal is predisposed to thedisease state but has not yet been diagnosed as having it; (b)inhibiting the disease state, i.e., arresting its development; and/or(c) achieving a full or partial reduction of the symptoms or diseasestate, and/or alleviating, ameliorating, lessening, or curing thedisease or disorder and/or its symptoms.

In view of their activity as selective inhibitors of TLR7, TLR8, orTLR9, compounds of Formula (I) are useful in treating TLR7, TLR8, orTLR9 family receptor associated diseases, but not limited to,inflammatory diseases such as Crohn's disease, ulcerative colitis,asthma, graft versus host disease, allograft rejection, chronicobstructive pulmonary disease; autoimmune diseases such as Graves'disease, rheumatoid arthritis, systemic lupus erythematosus, lupusnephritis, cutaneous lupus, psoriasis; auto-inflammatory diseasesincluding Cryopyrin-Associated Periodic Syndromes (CAPS), TNF ReceptorAssociated Periodic Syndrome (TRAPS), Familial Mediterranean Fever(FMF), adult onset stills, systemic onset juvenile idiopathic arthritis,gout, gouty arthritis; metabolic diseases including type 2 diabetes,atherosclerosis, myocardial infarction; destructive bone disorders suchas bone resorption disease, osteoarthritis, osteoporosis, multiplemyeloma-related bone disorder; proliferative disorders such as acutemyelogenous leukemia, chronic myelogenous leukemia; angiogenic disorderssuch as angiogenic disorders including solid tumors, ocularneovascularization, and infantile haemangiomas; infectious diseases suchas sepsis, septic shock, and Shigellosis; neurodegenerative diseasessuch as Alzheimer's disease, Parkinson's disease, cerebral ischemias orneurodegenerative disease caused by traumatic injury, oncologic andviral diseases such as metastatic melanoma, Kaposi's sarcoma, multiplemyeloma, and HIV infection and CMV retinitis, AIDS, respectively.

More particularly, the specific conditions or diseases that may betreated with the inventive compounds include, without limitation,pancreatitis (acute or chronic), asthma, allergies, adult respiratorydistress syndrome, chronic obstructive pulmonary disease,glomerulonephritis, rheumatoid arthritis, systemic lupus erythematosus,scleroderma, chronic thyroiditis, Graves' disease, autoimmune gastritis,diabetes, autoimmune hemolytic anemia, autoimmune neutropenia,thrombocytopenia, atopic dermatitis, chronic active hepatitis,myasthenia gravis, multiple sclerosis, inflammatory bowel disease,ulcerative colitis, Crohn's disease, psoriasis, graft vs. host disease,inflammatory reaction induced by endotoxin, tuberculosis,atherosclerosis, muscle degeneration, cachexia, psoriatic arthritis,Reiter's syndrome, gout, traumatic arthritis, rubella arthritis, acutesynovitis, pancreatic β-cell disease; diseases characterized by massiveneutrophil infiltration; rheumatoid spondylitis, gouty arthritis andother arthritic conditions, cerebral malaria, chronic pulmonaryinflammatory disease, silicosis, pulmonary sarcoidosis, bone resorptiondisease, allograft rejections, fever and myalgias due to infection,cachexia secondary to infection, keloid formation, scar tissueformation, ulcerative colitis, pyresis, influenza, osteoporosis,osteoarthritis, acute myelogenous leukemia, chronic myelogenousleukemia, metastatic melanoma, Kaposi's sarcoma, multiple myeloma,sepsis, septic shock, and Shigellosis; Alzheimer's disease, Parkinson'sdisease, cerebral ischemias or neurodegenerative disease caused bytraumatic injury; angiogenic disorders including solid tumors, ocularneovascularization, and infantile haemangiomas; viral diseases includingacute hepatitis infection (including hepatitis A, hepatitis B andhepatitis C), HIV infection and CMV retinitis, AIDS, ARC or malignancy,and herpes; stroke, myocardial ischemia, ischemia in stroke heartattacks, organ hypoxia, vascular hyperplasia, cardiac and renalreperfusion injury, thrombosis, cardiac hypertrophy, thrombin-inducedplatelet aggregation, endotoxemia and/or toxic shock syndrome,conditions associated with prostaglandin endoperoxidase syndase-2, andpemphigus vulgaris. Included in this embodiment are methods of treatmentin which the condition is selected from lupus including lupus nephritisand systemic lupus erythematosus (SLE), Crohn's disease, ulcerativecolitis, allograft rejection, rheumatoid arthritis, psoriasis,ankylosing spondylitis, psoriatic arthritis, and pemphigus vulgaris.Also included are methods of treatment in which the condition isselected from ischemia reperfusion injury, including cerebral ischemiareperfusions injury arising from stroke and cardiac ischemia reperfusioninjury arising from myocardial infarction. Another method of treatmentis one in which the condition is multiple myeloma.

In one embodiment, the compounds of Formula (I) are useful in treatingcancer, including Waldenstrom's Macroglobulinemia (WM), diffuse large Bcell lymphoma (DLBCL), chronic lymphocytic leukemia (CLL), cutaneousdiffuse large B cell lymphoma, and primary CNS lymphoma.

In addition, the TLR7, TLR8, or TLR9 inhibitors of the present inventioninhibit the expression of inducible pro-inflammatory proteins such asprostaglandin endoperoxide synthase-2 (PGHS-2), also referred to ascyclooxygenase-2 (COX-2), IL-1, IL-6, IL-18, chemokines. Accordingly,additional TLR7/8/9 associated conditions include edema, analgesia,fever and pain, such as neuromuscular pain, headache, pain caused bycancer, dental pain and arthritis pain. The inventive compounds also maybe used to treat veterinary viral infections, such as lentivirusinfections, including, but not limited to equine infectious anemiavirus; or retrovirus infections, including feline immunodeficiencyvirus, bovine immunodeficiency virus, and canine immunodeficiency virus.

The present invention thus provides methods for treating suchconditions, comprising administering to a subject in need thereof atherapeutically-effective amount of at least one compound of Formula (I)or a salt thereof “Therapeutically effective amount” is intended toinclude an amount of a compound of the present invention that iseffective when administered alone or in combination to inhibitautoimmune disease or chronic inflammatory disease.

The methods of treating TLR7, TLR8, or TLR9 associated conditions maycomprise administering compounds of Formula (I) alone or in combinationwith each other and/or other suitable therapeutic agents useful intreating such conditions. Accordingly, “therapeutically effectiveamount” is also intended to include an amount of the combination ofcompounds claimed that is effective to inhibit TLR7, TLR8, or TLR9and/or treat diseases associated with TLR7, TLR8, or TLR9.

Exemplary of such other therapeutic agents include corticosteroids,rolipram, calphostin, cytokine-suppressive anti-inflammatory drugs(CSAIDs), Interleukin-10, glucocorticoids, salicylates, nitric oxide,and other immunosuppressants; nuclear translocation inhibitors, such asdeoxyspergualin (DSG); non-steroidal anti-inflammatory drugs (NSAIDs)such as ibuprofen, celecoxib and rofecoxib; steroids such as prednisoneor dexamethasone; antiviral agents such as abacavir; antiproliferativeagents such as methotrexate, leflunomide, FK506 (tacrolimus, PROGRAF®);anti-malarials such as hydroxychloroquine; cytotoxic drugs such asazathiprine and cyclophosphamide; TNF-α inhibitors such as tenidap,anti-TNF antibodies or soluble TNF receptor, and rapamycin (sirolimus orRAPAMUNE®) or derivatives thereof.

The above other therapeutic agents, when employed in combination withthe compounds of the present invention, may be used, for example, inthose amounts indicated in the Physicians' Desk Reference (PDR) or asotherwise determined by one of ordinary skill in the art. In the methodsof the present invention, such other therapeutic agent(s) may beadministered prior to, simultaneously with, or following theadministration of the inventive compounds. The present invention alsoprovides pharmaceutical compositions capable of treating TLR7/8/9receptor-associated conditions, including IL-1 family receptor-mediateddiseases as described above.

The inventive compositions may contain other therapeutic agents asdescribed above and may be formulated, for example, by employingconventional solid or liquid vehicles or diluents, as well aspharmaceutical additives of a type appropriate to the mode of desiredadministration (e.g., excipients, binders, preservatives, stabilizers,flavors, etc.) according to techniques such as those well known in theart of pharmaceutical formulation.

Accordingly, the present invention further includes compositionscomprising one or more compounds of Formula (I) and a pharmaceuticallyacceptable carrier.

A “pharmaceutically acceptable carrier” refers to media generallyaccepted in the art for the delivery of biologically active agents toanimals, in particular, mammals. Pharmaceutically acceptable carriersare formulated according to a number of factors well within the purviewof those of ordinary skill in the art. These include without limitationthe type and nature of the active agent being formulated; the subject towhich the agent-containing composition is to be administered; theintended route of administration of the composition; and, thetherapeutic indication being targeted. Pharmaceutically acceptablecarriers include both aqueous and non-aqueous liquid media, as well as avariety of solid and semi-solid dosage forms. Such carriers can includea number of different ingredients and additives in addition to theactive agent, such additional ingredients being included in theformulation for a variety of reasons, e.g., stabilization of the activeagent, binders, etc., well known to those of ordinary skill in the art.Descriptions of suitable pharmaceutically acceptable carriers, andfactors involved in their selection, are found in a variety of readilyavailable sources such as, for example, Remington's PharmaceuticalSciences, 17th Edition (1985), which is incorporated herein by referencein its entirety.

Compounds in accordance with Formula (I) can be administered by anymeans suitable for the condition to be treated, which can depend on theneed for site-specific treatment or quantity of Formula (I) compound tobe delivered.

Also embraced within this invention is a class of pharmaceuticalcompositions comprising a compound of Formula (I) and one or morenon-toxic, pharmaceutically-acceptable carriers and/or diluents and/oradjuvants (collectively referred to herein as “carrier” materials) and,if desired, other active ingredients. The compounds of Formula (I) maybe administered by any suitable route, preferably in the form of apharmaceutical composition adapted to such a route, and in a doseeffective for the treatment intended. The compounds and compositions ofthe present invention may, for example, be administered orally,mucosally, or parenterally including intravascularly, intravenously,intraperitoneally, subcutaneously, intramuscularly, and intrasternallyin dosage unit formulations containing conventional pharmaceuticallyacceptable carriers, adjuvants, and vehicles. For example, thepharmaceutical carrier may contain a mixture of mannitol or lactose andmicrocrystalline cellulose. The mixture may contain additionalcomponents such as a lubricating agent, e.g. magnesium stearate and adisintegrating agent such as crospovidone. The carrier mixture may befilled into a gelatin capsule or compressed as a tablet. Thepharmaceutical composition may be administered as an oral dosage form oran infusion, for example.

For oral administration, the pharmaceutical composition may be in theform of, for example, a tablet, capsule, liquid capsule, suspension, orliquid. The pharmaceutical composition is preferably made in the form ofa dosage unit containing a particular amount of the active ingredient.For example, the pharmaceutical composition may be provided as a tabletor capsule comprising an amount of active ingredient in the range offrom about 0.1 to 1000 mg, preferably from about 0.25 to 250 mg, andmore preferably from about 0.5 to 100 mg. A suitable daily dose for ahuman or other mammal may vary widely depending on the condition of thepatient and other factors, but, can be determined using routine methods.

Any pharmaceutical composition contemplated herein can, for example, bedelivered orally via any acceptable and suitable oral preparations.Exemplary oral preparations, include, but are not limited to, forexample, tablets, troches, lozenges, aqueous and oily suspensions,dispersible powders or granules, emulsions, hard and soft capsules,liquid capsules, syrups, and elixirs. Pharmaceutical compositionsintended for oral administration can be prepared according to anymethods known in the art for manufacturing pharmaceutical compositionsintended for oral administration. In order to provide pharmaceuticallypalatable preparations, a pharmaceutical composition in accordance withthe invention can contain at least one agent selected from sweeteningagents, flavoring agents, coloring agents, demulcents, antioxidants, andpreserving agents.

A tablet can, for example, be prepared by admixing at least one compoundof Formula (I) with at least one non-toxic pharmaceutically acceptableexcipient suitable for the manufacture of tablets. Exemplary excipientsinclude, but are not limited to, for example, inert diluents, such as,for example, calcium carbonate, sodium carbonate, lactose, calciumphosphate, and sodium phosphate; granulating and disintegrating agents,such as, for example, microcrystalline cellulose, sodiumcrosscarmellose, corn starch, and alginic acid; binding agents, such as,for example, starch, gelatin, polyvinyl-pyrrolidone, and acacia; andlubricating agents, such as, for example, magnesium stearate, stearicacid, and talc. Additionally, a tablet can either be uncoated, or coatedby known techniques to either mask the bad taste of an unpleasanttasting drug, or delay disintegration and absorption of the activeingredient in the gastrointestinal tract thereby sustaining the effectsof the active ingredient for a longer period. Exemplary water solubletaste masking materials, include, but are not limited to,hydroxypropyl-methylcellulose and hydroxypropyl-cellulose. Exemplarytime delay materials, include, but are not limited to, ethyl celluloseand cellulose acetate butyrate.

Hard gelatin capsules can, for example, be prepared by mixing at leastone compound of Formula (I) with at least one inert solid diluent, suchas, for example, calcium carbonate; calcium phosphate; and kaolin.

Soft gelatin capsules can, for example, be prepared by mixing at leastone compound of Formula (I) with at least one water soluble carrier,such as, for example, polyethylene glycol; and at least one oil medium,such as, for example, peanut oil, liquid paraffin, and olive oil.

An aqueous suspension can be prepared, for example, by admixing at leastone compound of Formula (I) with at least one excipient suitable for themanufacture of an aqueous suspension. Exemplary excipients suitable forthe manufacture of an aqueous suspension, include, but are not limitedto, for example, suspending agents, such as, for example, sodiumcarboxymethylcellulose, methylcellulose, hydroxypropylmethyl-cellulose,sodium alginate, alginic acid, polyvinyl-pyrrolidone, gum tragacanth,and gum acacia; dispersing or wetting agents, such as, for example, anaturally-occurring phosphatide, e.g., lecithin; condensation productsof alkylene oxide with fatty acids, such as, for example,polyoxyethylene stearate; condensation products of ethylene oxide withlong chain aliphatic alcohols, such as, for exampleheptadecaethylene-oxycetanol;

condensation products of ethylene oxide with partial esters derived fromfatty acids and hexitol, such as, for example, polyoxyethylene sorbitolmonooleate; and condensation products of ethylene oxide with partialesters derived from fatty acids and hexitol anhydrides, such as, forexample, polyethylene sorbitan monooleate. An aqueous suspension canalso contain at least one preservative, such as, for example, ethyl andn-propyl p-hydroxybenzoate; at least one coloring agent; at least oneflavoring agent; and/or at least one sweetening agent, including but notlimited to, for example, sucrose, saccharin, and aspartame.

Oily suspensions can, for example, be prepared by suspending at leastone compound of Formula (I) in either a vegetable oil, such as, forexample, arachis oil; olive oil; sesame oil; and coconut oil; or inmineral oil, such as, for example, liquid paraffin. An oily suspensioncan also contain at least one thickening agent, such as, for example,beeswax; hard paraffin; and cetyl alcohol. In order to provide apalatable oily suspension, at least one of the sweetening agents alreadydescribed hereinabove, and/or at least one flavoring agent can be addedto the oily suspension. An oily suspension can further contain at leastone preservative, including, but not limited to, for example, ananti-oxidant, such as, for example, butylated hydroxyanisol, andalpha-tocopherol.

Dispersible powders and granules can, for example, be prepared byadmixing at least one compound of Formula (I) with at least onedispersing and/or wetting agent; at least one suspending agent; and/orat least one preservative. Suitable dispersing agents, wetting agents,and suspending agents are as already described above. Exemplarypreservatives include, but are not limited to, for example,anti-oxidants, e.g., ascorbic acid. In addition, dispersible powders andgranules can also contain at least one excipient, including, but notlimited to, for example, sweetening agents; flavoring agents; andcoloring agents.

An emulsion of at least one compound of Formula (I) thereof can, forexample, be prepared as an oil-in-water emulsion. The oily phase of theemulsions comprising compounds of Formula (I) may be constituted fromknown ingredients in a known manner. The oil phase can be provided by,but is not limited to, for example, a vegetable oil, such as, forexample, olive oil and arachis oil; a mineral oil, such as, for example,liquid paraffin; and mixtures thereof. While the phase may comprisemerely an emulsifier, it may comprise a mixture of at least oneemulsifier with a fat or an oil or with both a fat and an oil. Suitableemulsifying agents include, but are not limited to, for example,naturally-occurring phosphatides, e.g., soy bean lecithin; esters orpartial esters derived from fatty acids and hexitol anhydrides, such as,for example, sorbitan monooleate; and condensation products of partialesters with ethylene oxide, such as, for example, polyoxyethylenesorbitan monooleate. Preferably, a hydrophilic emulsifier is includedtogether with a lipophilic emulsifier which acts as a stabilizer. It isalso preferred to include both an oil and a fat. Together, theemulsifier(s) with or without stabilizer(s) make-up the so-calledemulsifying wax, and the wax together with the oil and fat make up theso-called emulsifying ointment base which forms the oily dispersed phaseof the cream formulations. An emulsion can also contain a sweeteningagent, a flavoring agent, a preservative, and/or an antioxidant.Emulsifiers and emulsion stabilizers suitable for use in the formulationof the present invention include Tween 60, Span 80, cetostearyl alcohol,myristyl alcohol, glyceryl monostearate, sodium lauryl sulfate, glyceryldistearate alone or with a wax, or other materials well known in theart.

The compounds of Formula (I) can, for example, also be deliveredintravenously, subcutaneously, and/or intramuscularly via anypharmaceutically acceptable and suitable injectable form. Exemplaryinjectable forms include, but are not limited to, for example, sterileaqueous solutions comprising acceptable vehicles and solvents, such as,for example, water, Ringer's solution, and isotonic sodium chloridesolution; sterile oil-in-water microemulsions; and aqueous or oleaginoussuspensions.

Formulations for parenteral administration may be in the form of aqueousor non-aqueous isotonic sterile injection solutions or suspensions.These solutions and suspensions may be prepared from sterile powders orgranules using one or more of the carriers or diluents mentioned for usein the formulations for oral administration or by using other suitabledispersing or wetting agents and suspending agents. The compounds may bedissolved in water, polyethylene glycol, propylene glycol, ethanol, cornoil, cottonseed oil, peanut oil, sesame oil, benzyl alcohol, sodiumchloride solution, tragacanth gum, and/or various buffers. Otheradjuvants and modes of administration are well and widely known in thepharmaceutical art. The active ingredient may also be administered byinjection as a composition with suitable carriers including saline,dextrose, or water, or with cyclodextrin (i.e. Captisol), cosolventsolubilization (i.e. propylene glycol) or micellar solubilization (i.e.Tween 80).

The sterile injectable preparation may also be a sterile injectablesolution or suspension in a non-toxic parenterally acceptable diluent orsolvent, for example as a solution in 1,3-butanediol. Among theacceptable vehicles and solvents that may be employed are water,Ringer's solution, and isotonic sodium chloride solution. In addition,sterile, fixed oils are conventionally employed as a solvent orsuspending medium. For this purpose any bland fixed oil may be employed,including synthetic mono- or diglycerides. In addition, fatty acids suchas oleic acid find use in the preparation of injectables.

A sterile injectable oil-in-water microemulsion can, for example, beprepared by 1) dissolving at least one compound of Formula (I) in anoily phase, such as, for example, a mixture of soybean oil and lecithin;2) combining the Formula (I) containing oil phase with a water andglycerol mixture; and 3) processing the combination to form amicroemulsion.

A sterile aqueous or oleaginous suspension can be prepared in accordancewith methods already known in the art. For example, a sterile aqueoussolution or suspension can be prepared with a non-toxicparenterally-acceptable diluent or solvent, such as, for example,1,3-butane diol; and a sterile oleaginous suspension can be preparedwith a sterile non-toxic acceptable solvent or suspending medium, suchas, for example, sterile fixed oils, e.g., synthetic mono- ordiglycerides; and fatty acids, such as, for example, oleic acid.

Pharmaceutically acceptable carriers, adjuvants, and vehicles that maybe used in the pharmaceutical compositions of this invention include,but are not limited to, ion exchangers, alumina, aluminum stearate,lecithin, self-emulsifying drug delivery systems (SEDDS) such asd-alpha-tocopherol polyethyleneglycol 1000 succinate, surfactants usedin pharmaceutical dosage forms such as Tweens, polyethoxylated castoroil such as CREMOPHOR surfactant (BASF), or other similar polymericdelivery matrices, serum proteins, such as human serum albumin, buffersubstances such as phosphates, glycine, sorbic acid, potassium sorbate,partial glyceride mixtures of saturated vegetable fatty acids, water,salts or electrolytes, such as protamine sulfate, disodium hydrogenphosphate, potassium hydrogen phosphate, sodium chloride, zinc salts,colloidal silica, magnesium trisilicate, polyvinyl pyrrolidone,cellulose-based substances, polyethylene glycol, sodiumcarboxymethylcellulose, polyacrylates, waxes,polyethylene-polyoxypropylene-block polymers, polyethylene glycol andwool fat. Cyclodextrins such as alpha-, beta-, and gamma-cyclodextrin,or chemically modified derivatives such as hydroxyalkylcyclodextrins,including 2- and 3-hydroxypropyl-cyclodextrins, or other solubilizedderivatives may also be advantageously used to enhance delivery ofcompounds of the formulae described herein.

The pharmaceutically active compounds of this invention can be processedin accordance with conventional methods of pharmacy to produce medicinalagents for administration to patients, including humans and othermammals. The pharmaceutical compositions may be subjected toconventional pharmaceutical operations such as sterilization and/or maycontain conventional adjuvants, such as preservatives, stabilizers,wetting agents, emulsifiers, buffers etc. Tablets and pills canadditionally be prepared with enteric coatings. Such compositions mayalso comprise adjuvants, such as wetting, sweetening, flavoring, andperfuming agents.

The amounts of compounds that are administered and the dosage regimenfor treating a disease condition with the compounds and/or compositionsof this invention depends on a variety of factors, including the age,weight, sex, the medical condition of the subject, the type of disease,the severity of the disease, the route and frequency of administration,and the particular compound employed. Thus, the dosage regimen may varywidely, but can be determined routinely using standard methods. A dailydose of about 0.001 to 100 mg/kg body weight, preferably between about0.0025 and about 50 mg/kg body weight and most preferably between about0.005 to 10 mg/kg body weight, may be appropriate. The daily dose can beadministered in one to four doses per day. Other dosing schedulesinclude one dose per week and one dose per two day cycle.

For therapeutic purposes, the active compounds of this invention areordinarily combined with one or more adjuvants appropriate to theindicated route of administration. If administered orally, the compoundsmay be admixed with lactose, sucrose, starch powder, cellulose esters ofalkanoic acids, cellulose alkyl esters, talc, stearic acid, magnesiumstearate, magnesium oxide, sodium and calcium salts of phosphoric andsulfuric acids, gelatin, acacia gum, sodium alginate,polyvinylpyrrolidone, and/or polyvinyl alcohol, and then tableted orencapsulated for convenient administration. Such capsules or tablets maycontain a controlled-release formulation as may be provided in adispersion of active compound in hydroxypropylmethyl cellulose.

Pharmaceutical compositions of this invention comprise at least onecompound of Formula (I) and optionally an additional agent selected fromany pharmaceutically acceptable carrier, adjuvant, and vehicle.Alternate compositions of this invention comprise a compound of theFormula (I) described herein, or a prodrug thereof, and apharmaceutically acceptable carrier, adjuvant, or vehicle.

The present invention also encompasses an article of manufacture. Asused herein, article of manufacture is intended to include, but not belimited to, kits and packages. The article of manufacture of the presentinvention, comprises: (a) a first container; (b) a pharmaceuticalcomposition located within the first container, wherein the composition,comprises: a first therapeutic agent, comprising: a compound of thepresent invention or a pharmaceutically acceptable salt form thereof;and (c) a package insert stating that the pharmaceutical composition canbe used for the treatment of an inflammatory disorder and/or anautoimmune disease (as defined previously). In another embodiment, thepackage insert states that the pharmaceutical composition can be used incombination (as defined previously) with a second therapeutic agent totreat an inflammatory disorder and/or an autoimmune disease. The articleof manufacture can further comprise: (d) a second container, whereincomponents (a) and (b) are located within the second container andcomponent (c) is located within or outside of the second container.Located within the first and second containers means that the respectivecontainer holds the item within its boundaries.

The first container is a receptacle used to hold a pharmaceuticalcomposition. This container can be for manufacturing, storing, shipping,and/or individual/bulk selling. First container is intended to cover abottle, jar, vial, flask, syringe, tube (e.g., for a cream preparation),or any other container used to manufacture, hold, store, or distribute apharmaceutical product.

The second container is one used to hold the first container and,optionally, the package insert. Examples of the second containerinclude, but are not limited to, boxes (e.g., cardboard or plastic),crates, cartons, bags (e.g., paper or plastic bags), pouches, and sacks.The package insert can be physically attached to the outside of thefirst container via tape, glue, staple, or another method of attachment,or it can rest inside the second container without any physical means ofattachment to the first container. Alternatively, the package insert islocated on the outside of the second container. When located on theoutside of the second container, it is preferable that the packageinsert is physically attached via tape, glue, staple, or another methodof attachment. Alternatively, it can be adjacent to or touching theoutside of the second container without being physically attached.

The package insert is a label, tag, marker, etc. that recitesinformation relating to the pharmaceutical composition located withinthe first container. The information recited will usually be determinedby the regulatory agency governing the area in which the article ofmanufacture is to be sold (e.g., the United States Food and DrugAdministration). In one embodiment, the package insert specificallyrecites the indications for which the pharmaceutical composition hasbeen approved. The package insert may be made of any material on which aperson can read information contained therein or thereon. For example,the package insert is a printable material (e.g., paper, plastic,cardboard, foil, adhesive-backed paper or plastic, etc.) on which thedesired information has been formed (e.g., printed or applied).

Methods of Preparation

The compounds of the present invention can be prepared in a number ofways well known to one skilled in the art of organic synthesis. Thecompounds of the present invention can be synthesized using the methodsdescribed below, together with synthetic methods known in the art ofsynthetic organic chemistry, or variations thereon as appreciated bythose skilled in the art. Preferred methods include, but are not limitedto, those described below. All references cited herein are herebyincorporated in their entirety by reference.

The compounds of this invention may be prepared using the reactions andtechniques described in this section. The reactions are performed insolvents appropriate to the reagents and materials employed and aresuitable for the transformations being effected. Also, in thedescription of the synthetic methods described below, it is to beunderstood that all proposed reaction conditions, including choice ofsolvent, reaction atmosphere, reaction temperature, duration of theexperiment and work up procedures, are chosen to be the conditionsstandard for that reaction, which should be readily recognized by oneskilled in the art. It is understood by one skilled in the art oforganic synthesis that the functionality present on various portions ofthe molecule must be compatible with the reagents and reactionsproposed. Such restrictions to the substituents that are compatible withthe reaction conditions will be readily apparent to one skilled in theart and alternate methods must then be used. This will sometimes requirea judgment to modify the order of the synthetic steps or to select oneparticular process scheme over another in order to obtain a desiredcompound of the invention. It will also be recognized that another majorconsideration in the planning of any synthetic route in this field isthe judicious choice of the protecting group used for protection of thereactive functional groups present in the compounds described in thisinvention. An authoritative account describing the many alternatives tothe trained practitioner is Greene and Wuts (Protective Groups InOrganic Synthesis, Third Edition, Wiley and Sons, 1999).

EXAMPLES

Preparation of compounds of Formula (I), and intermediates used in thepreparation of compounds of Formula (I), can be prepared usingprocedures shown in the following Examples and related procedures. Themethods and conditions used in these examples, and the actual compoundsprepared in these Examples, are not meant to be limiting, but are meantto demonstrate how the compounds of Formula (I) can be prepared.Starting materials and reagents used in these examples, when notprepared by a procedure described herein, are generally eithercommercially available, or are reported in the chemical literature, ormay be prepared by using procedures described in the chemicalliterature.

ABBREVIATIONS

-   Ac acetyl-   ACN acetonitrile-   anhyd. anhydrous-   aq. aqueous-   BINAP 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl-   Bn benzyl-   Bu butyl-   Boc tert-butoxycarbonyl-   CDI carbonyldiimidazole-   DCM dichloromethane-   DMF dimethylformamide-   DMSO dimethylsulfoxide-   EA ethyl acetate-   EtOAc ethyl acetate-   Et ethyl-   H or H₂ hydrogen-   h, hr or hrs hour(s)-   HATU O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium    hexafluorophosphate-   hex hexane-   Hz Hertz-   i iso-   HOAc/AcOH acetic acid-   HCl hydrochloric acid-   HPLC high pressure liquid chromatography-   LC liquid chromatography-   LCMS liquid chromatography mass spectroscopy-   LCMS RT liquid chromatography mass spectroscopy retention time-   M molar-   mM millimolar-   Me methyl-   MeOH methanol-   MHz megahertz-   min. minute(s)-   mins minute(s)-   M⁺¹ (M+H)⁺-   MS mass spectrometry-   n or N normal-   NB S n-bromosuccinimide-   NH₄OAc ammonium acetate-   nm nanometer-   nM nanomolar-   Pd/C palladium on carbon-   PdCl₂(dppf)    [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II)-   Pet ether petroleum ether-   Ph phenyl-   RT (min) retention time (minutes)-   sat. saturated-   tBu tertiary butyl-   TEA triethylamine-   TFA trifluoroacetic acid-   THF tetrahydrofuran

Analytical LCMS/HPLC Conditions:

(A) Column: Acquity UPLC BEH C18, 3.0×50 mm, 1.7 μm particles; MobilePhase A: 5:95 acetonitrile:water with 5 mM ammonium acetate; MobilePhase B: 95:5 acetonitrile:water with 5 mM ammonium acetate; Method: %B: 0 min-20%:1.1 min 90%:1.7 min-90%; Flow: 0.7 mL/min.(B) Kinetex XB-C18 (75×3 mm) 2.6 micron; Solvent A: 10 mM ammoniumformate in water:acetonitrile (98:2); Mobile Phase B: 10 mM ammoniumformate in water:acetonitrile (02:98); Temperature: 50° C.; Gradient:0-100% B over 3 minutes; Flow rate: 1.1 mL/min; Detection: UV at 220 nm.(C) Waters)(Bridge BEH C18 XP (50×2.1 mm) 2.5 μm; Mobile Phase A: 5:95acetonitrile:water with 10 mM NH₄OAc; Mobile Phase B: 95:5acetonitrile:water with 10 mM NH₄OAc; Temperature: 50° C.; Gradient:0-100% B over 3 minutes; Flow: 1.1 mL/min.(D) Waters)(Bridge BEH C18 XP (50×2.1 mm) 2.5 μm; Mobile Phase A: 5:95acetonitrile:water with 0.1% TFA; Mobile Phase B: 95:5acetonitrile:water with 0.1% TFA; Temperature: 50° C.; Gradient: 0-100%B over 3 minutes; Flow: 1.1 mL/min.(E) Ascentis Express C18 (50×2.1 mm), 2.7 μm; Mobile Phase A: 5:95acetonitrile:water with 10 mM NH₄OAc; Mobile Phase B: 95:5acetonitrile:water with 10 mM NH₄OAc; Temperature: 50° C.; Gradient:0-100% B over 3 minutes; Flow: 1.1 mL/min.(F) Ascentis Express C18 (50×2.1 mm), 2.7 μm; Mobile Phase A: 5:95acetonitrile:water with 0.1% TFA; Mobile Phase B: 95:5acetonitrile:water with 0.1% TFA; Temperature: 50° C.; Gradient:0-100% Bover 3 minutes; Flow: 1.1 mL/min.(G) Column: Waters Acquity UPLC BEH C18 (2.1×50 mm), 1.7 micron; SolventA=100% water with 0.05% TFA; Solvent B=100% acetonitrile with 0.05% TFA;gradient=2-98% B over 1 minute, then a 0.5-minute hold at 98% B; Flowrate: 0.8 mL/min; Detection: UV at 220 nm.(H) Column: ZORBAX SB AQ (4.6×50) mm, 3.5 micron, Solvent A:acetonitrile (98:2); Mobile Phase B: 10 mM ammonium formate inwater:acetonitrile (2:98); Temperature: 50° C.; Gradient: 0-100% B over3 minutes; Flow rate: 1.1 mL/min; Detection: UV at 220 nm.(I) Kinetex XB-C18 (75×3 mm) 2.6 micron; Solvent A: 0.1% TFA inwater:acetonitrile (98:2); Mobile Phase B: 10 mM ammonium formate inwater:acetonitrile (2:98); Temperature: 50° C.; Gradient: 0-100% B over3 minutes; Flow rate: 1.1 mL/min; Detection: UV at 220 nm.

Prep Purification Conditions

Method AA: Waters)(Bridge C18, 19×150 mm, 5 μm particles; Mobile PhaseA: 10 mM ammonium acetate; Mobile Phase B: methanol; Gradient: 10-45% Bover 20 minutes, then a 5-minutehold at 100% B; Flow: 20 mL/min.Method AB: Waters)(Bridge C18, 19×150 mm, 5 μm particles; Mobile PhaseA: 0.1% trifluoroacetic acid; Mobile Phase B: acetonitrile; Gradient:5-25% B over 25 minutes, then a 5-minutehold at 100% B; Flow: 15 mL/min.

Example 15-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1-(1-methylpiperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one

Intermediate 1A: tert-butyl4-((4-bromo-5-methyl-2-nitrophenyl)amino)piperidine-1-carboxylate

To a mixture of 1-bromo-4-fluoro-2-methyl-5-nitrobenzene (0.500 g, 2.137mmol) and tert-butyl 4-aminopiperidine-1-carboxylate (0.513 g, 2.56mmol) in DMF (10.0 mL) was added K₂CO₃ (0.591 g, 4.27 mmol). The mixturewas stirred at 90° C. for 3 h. The reaction mixture was diluted withwater (20 mL), the precipitated solids were filtered, washed with water(2×10 mL) and dried under vacuum to afford tert-butyl4-((4-bromo-5-methyl-2-nitrophenyl)amino)piperidine-1-carboxylate (0.824g, 1.989 mmol, 93% yield) as a yellow color solid. LCMS retention time1.71 min [A], MS (ES): m/z=360.4 [M+2H-tBu].

The following Intermediates were prepared according to the procedureused to prepare Intermediate 1A.

TABLE 1 Mol RT HPLC Intermediate Structure Wt. LCMS (min) Method 1AB

414.3 360.1 [M − tBu + 2H] 3.880 B 1AC

414.3 360.0 [M − tBu + 2H] 3.960 B 1AD

400.2 346.1 [M − tBu + 2H] 1.86  A 1AE

428.3 430.4 [M + 2H] 1.76  A Cis Isomer 1AF

428.3 430.3 [M + 2H] 1.83  A Trans Isomer

Intermediate 1B: tert-butyl4-((4-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-5-methyl-2-nitrophenyl)amino)piperidine-1-carboxylate

A mixture of tert-butyl4-((4-bromo-5-methyl-2-nitrophenyl)amino)piperidine-1-carboxylate (0.400g, 0.965 mmol),8-methoxy-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-[1,2,4]triazolo[1,5-a]pyridine(0.398 g, 1.448 mmol) and potassium phosphate tribasic (0.615 g, 2.90mmol) in dioxane (15.0 mL) and water (5.0 mL) was degassed for 10 min,then PdCl₂(dppf)-CH₂Cl₂ adduct (0.079 g, 0.097 mmol) was added. Thesolution was again degassed for 2 min, and the mixture was stirred at90° C. for 2 h.

The reaction mixture was brought to room temperature, diluted with DCM(20 mL) and water (10 mL), separated both the layers, the aqueous layerwas extracted with 10% MeOH in DCM (2×30 mL), the combined organicextracts were dried (Na₂SO₄) and concentrated to afford crude compound.The crude was purified by ISCO using 24 g silica column, compound waseluted in EA, the fractions were collected and concentrated to affordtert-butyl4-((4-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-5-methyl-2-nitrophenyl)amino)piperidine-1-carboxylate(0.423 g, 0.877 mmol, 91% yield) as an off-white solid. LCMS retentiontime 1.35 min [A], MS (ES): m/z=483.6 [M+H].

The following Intermediates were prepared according to the procedureused to prepare Intermediate 1B.

TABLE 2 LCMS RT HPLC Intermediate Structure MH⁺ (min) Method 1BA

437.6 1.20  A 1BB

467.2 3.204 B 1BC

467.2 3.062 B 1BD

453.5 1.50  A 1BE

469.1 1.79  A 1BF

483.1 3.047 B 1BG

481.6 1.43  A Cis Isomer 1BH

481.4 1.38  A Trans Isomer 1BI

497.5 1.72  A Cis Isomer

Intermediate 1C: tert-butyl4-((2-amino-4-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-5-methylphenyl)amino)piperidine-1-carboxylate

To a solution of tert-butyl4-((4-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-5-methyl-2-nitrophenyl)amino)piperidine-1-carboxylate(0.420 g, 0.870 mmol) in MeOH (9.00 mL) was added Pd/C (0.093 g, 0.870mmol) at room temperature. The mixture was stirred at same temperatureunder hydrogen bladder for 3 h. The reaction mass was filtered throughcelite, washed with MeOH, concentrated the filtrates and dried undervacuum to afford tert-butyl4-((2-amino-4-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-5-methylphenyl)amino)piperidine-1-carboxylate (0.384 g, 0.849 mmol, 97% yield) as anoff-white solid. LCMS retention time 1.17 min [A], MS (ES): m/z=453.6[M+H].

Intermediate 1D: tert-butyl4-(5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidine-1-carboxylate

To a solution of tert-butyl4-((2-amino-4-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-5-methylphenyl)amino)piperidine-1-carboxylate(0.313 g, 0.692 mmol) in acetonitrile (15.00 mL) was added CDI (0.168 g,1.037 mmol) at room temperature. The mixture was stirred at the sametemperature for 16 h. The reaction mass was concentrated to afford crudecompound, the crude was purified by ISCO using 12 g silica column,compound was eluted in EA, the fractions were collected and concentratedto afford tert-butyl4-(5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidine-1-carboxylate (0.303 g, 0.633 mmol, 92% yield) as a whitesolid. LCMS retention time 1.07 min [A], MS (ES): m/z=479.5 [M+H].

Intermediate 1E:5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1-(piperidin-4-yl)-1H-benzo[d]imidazol-2(3H)-one,TFA

To a solution of tert-butyl4-(5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidine-1-carboxylate(0.350 g, 0.731 mmol) in DCM (10.0 mL) was added TFA (1.00 mL) at 0° C.The mixture was stirred at same temperature for 1 h. Volatiles wereremoved by blowing with nitrogen gas and dried under vacuum to affordcrude compound. The crude material was triturated with diethyl ether(2×10 mL), then dried under vacuum to afford5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1-(piperidin-4-yl)-1H-benzo[d]imidazol-2(3H)-one,TFA (0.330 g, 0.671 mmol, 92% yield) as a white solid. LCMS retentiontime 0.49 [A], MS (ES): m/z=379.6 [M+H]; ¹H NMR (400 MHz, METHANOL-d₄) δppm 8.38 (s, 1H), 8.32 (s, 1H), 7.28 (s, 1H), 7.06-7.03 (m, 2H), 4.07(s, 3H), 3.60-3.55 (m, 2H), 3.36-3.34 (m, 1H), 3.24-3.16 (m, 2H),2.77-2.68 (m, 2H), 2.37 (s, 3H), 2.10-2.02 (m, 2H).

The following intermediates were prepared according to the procedureused to prepare intermediate 1E

TABLE 3 Interme- Mol LCMS RT HPLC diate Structure Wt. MH⁺ (min) Method1EA

362.4 363.2 0.705 E 1EB

348.4 349.1 0.66 E 1EC

362.4 363.3 0.89 E 1ED

362.4 363.2 0.9 E 1EE

376.5 377.2 0.932 E 1EF

376.5 377.2 0.79 E 1EG

392.5 393.2 0.847 E 1EH

378.4 379.2 0.72 E 1EI

364.4 365.2 0.82 E

Example 1:5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1-(1-methylpiperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one

To a solution of5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1-(piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(0.024 g, 0.063 mmol) in MeOH (2.00 mL) was added formaldehyde in water(0.2 mL, 2.178 mmol). The reaction mixture was stirred for 5 min, aceticacid (0.1 mL, 1.747 mmol) was added, and the reaction mixture wasstirred at room temperature for 6 h. Next, sodium cyanoborohydride(0.012 g, 0.190 mmol) was added and the reaction mixture was stirred foranother 16 h. The reaction mass was purified by Prep LCMS using methodAA, fractions containing the product were combined and dried usingGenevac centrifugal evaporator to afford5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1-(1-methylpiperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(0.0031 g, 7.82 μmol, 12.33% yield) as a pale solid. LCMS RT=0.806 min[E], MS (ES): m/z=393.2 [M+H]; ¹H NMR (400 MHz, METHANOL-d₄) δ ppm 8.40(s, 1H), 8.34 (s, 1H), 7.38 (s, 1H), 7.06 (s, 2H), 4.42 (s, 1H), 4.09(s, 3H), 3.23 (d, J=11.0 Hz, 2H), 2.70-2.60 (m, 2H), 2.53 (s, 5H), 2.38(s, 3H), 1.90 (d, J=13.9 Hz, 2H).

The following examples were prepared according to the general procedureused to prepare Example 1.

TABLE 4 Ex LCMS RT HPLC No. Structure MH⁺ (Min) Method 2

405.3 0.911 E 3

377.2 0.853 E 4

363.3 0.77 E 5

391.2 0.82 E 6

391.3 0.901 E 7

405.2 1.047 E 9

407.3 0.748 F 10

421.3 0.804 F 11

377.3 1.09 E 12

391.3 1.13 E 13

405.3 1.17 E 14

419.2 1.2 E 15

377.2 1.08 E 16

391.2 1.12 E 17

405.2 1.17 E 18

419.2 1.2 E 19

405.2 1.05 E 20

433.2 1.18 E 21

405.2 1.04 E 22

419.2 1.1 E 23

405.2 0.96 E 24

405.2 0.94 E 25

419.2 1.03 E 26

433.3 1.95 E 27

447.3 1.21 E 28

419.3 1.01 F 29

459.2 1.64 E 30

461.2 1.09 E 31

473.2 1.63 E 32

447.2 1.68 E 33

472.2 1.11 E 34

433.2 1.19 E 35

458.3 0.87 D 36

485.3 1.365 C 37

417.2 1.289 C 38

433.3 1.595 C 39

473.3 1.706 C 40

419.2 1.532 C 41

461.3 0.948 D 42

405.3 0.954 D 43

447.2 1.32 C 44

447.3 1.686 C 45

447.3 1.248 D 46

454.2 1.346 C 47

445.36 1.62 C 48

421.2 0.89 E 49

477.2 0.96 E 50

435.2 0.929 E 51

393.3 0.93 E 52

407.3 0.97 E 53

421.2 0.99 E 54

421.2 1.14 E 55

433.3 1.13 E 56

435.3 1.49 E 57

477.3 1.31 E 58

447.2 1.06 D 59

449.2 0.89 C 60

447.2 1.06 C 61

449.3 1.27 C 62

475.3 1.22 D 63

421.2 0.95 D 64

435.3 1.04 C 65

461.3 1.13 C 66

489.3 1.56 C 67

449.3 1.31 D 68

475.2 1.76 C 69

433.2 1.23 D 70

463.2 1.18 C 71

449.3 1.32 C 72

435.2 1.14 C 73

463.2 1.41 C 74

379.2 0.84 E 75

449.2 1.57 E 76

407.2 1 E 77

407.2 0.96 E 78

463.2 1.1 E 79

419.2 1.03 E 80

421.2 1.02 E 81

435.2 1.04 E 82

449.2 1.06 E 83

419.2 1.09 E

Example 841-((1s,4s)-4-(isopropyl(methyl)amino)cyclohexyl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1,3-dihydro-2H-benzo[d]imidazol-2-one

To a stirred solution of1-((1s,4s)-4-(isopropylamino)cyclohexyl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1,3-dihydro-2H-benzo[d]imidazol-2-one(50 mg, 0.115 mmol) in THF (1 mL) and DMF (1 mL) were added formaldehyde(3.45 mg, 0.115 mmol) and acetic acid (6.59 μL, 0.115 mmol). Thereaction mixture was stirred at room temperature for 16 h, then NaCNBH₃(7.23 mg, 0.115 mmol) was added. The reaction mixture was stirred foranother 2 h. The reaction mass was purified by Prep LCMS using methodAA, fractions containing the product were combined and dried usingGenevac centrifugal evaporator to afford1-((1s,4s)-4-(isopropyl(methyl)amino)cyclohexyl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1,3-dihydro-2H-benzo[d]imidazol-2-one(3.1 mg) as an off-white solid. LCMS retention time 1.025 min [A], MS(ES): m/z=449.3 [M+H]; ¹H NMR (400 MHz, DMSO-d₆) δ 10.83 (s, 1H), 8.50(d, J=1.2 Hz, 1H), 8.45 (s, 1H), 7.26 (s, 1H), 7.06 (d, J=1.2 Hz, 1H),6.94 (s, 1H), 4.39-4.30 (m, 1H), 4.06-3.96 (m, 3H), 3.28-3.24 (m, 1H),2.47-2.34 (m, 2H), 2.28 (s, 3H), 2.14 (s, 3H), 2.09 (d, J=13.4 Hz, 2H),1.90 (s, 1H), 1.52 (t, J=13.6 Hz, 2H), 1.42 (d, J=8.3 Hz, 2H), 1.04 (d,J=6.4 Hz, 6H).

Example 855-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1-((1s,4s)-4-(methyl(tetrahydro-2H-pyran-4-yl)amino)cyclohexyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one

5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1-((1s,4s)-4-(methyl(tetrahydro-2H-pyran-4-yl)amino)cyclohexyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(6 mg) was prepared according to the general procedure described inExample 84 using5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1-((1s,4s)-4-((tetrahydro-2H-pyran-4-yl)amino)cyclohexyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(30 mg, 0.063 mmol) as a starting intermediate to afford the titlecompound as a white solid. LCMS retention time 1.10 min [A], MS (ES):m/z=491.3 [M+H]; ¹H NMR (400 MHz, DMSO-d₆) δ 10.88 (s, 1H), 9.05 (br.s., 1H), 8.57-8.38 (m, 2H), 8.29 (br. s., 1H), 7.34-7.19 (m, 1H), 7.14(s, 1H), 7.06-6.96 (m, 1H), 6.94 (s, 1H), 4.37 (br. s., 1H), 4.10-3.89(m, 4H), 3.69 (br. s., 1H), 3.63 (br. s., 1H), 3.52-3.39 (m, 2H), 2.94(dd, J=12.5, 6.8 Hz, 1H), 2.78 (d, J=4.9 Hz, 2H), 2.45-2.15 (m, 6H),2.10-1.99 (m, 1H), 1.93 (d, J=10.0 Hz, 2H), 1.84 (d, J=12.2 Hz, 2H),1.69 (dd, J=12.5, 4.4 Hz, 1H), 1.17 (t, J=7.3 Hz, 1H).

Example 862-(4-(5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidin-1-yl)-N,N-dimethylacetamide

To a solution of5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1-(piperidin-4-yl)-1H-benzo[d]imidazol-2(3H)-one,TFA (0.030 g, 0.061 mmol) and 2-chloro-N,N-dimethylacetamide (0.015 g,0.122 mmol) in THF (1.00 mL) and DMF (0.50 mL) solvent mixture was addedTEA (0.1 mL, 0.717 mmol) at room temperature. The reaction mixture wasstirred at the same temperature for 16 h. The reaction mass was purifiedby Prep LCMS using method AA, fractions containing the product werecombined and dried using Genevac centrifugal evaporator to afford2-(4-(5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidin-1-yl)-N,N-dimethylacetamide(0.0058 g, 0.012 mmol, 20% yield) as a pale solid. LCMS retention time0.983 min [E], MS (ES): m/z=464.3 [M+H]; ¹H NMR (400 MHz, METHANOL-d₄) δppm 8.40 (s, 1H), 8.35 (d, J=1.5 Hz, 1H), 7.49 (s, 1H), 7.12-7.01 (m,2H), 4.91 (s, 2H), 4.47-4.29 (m, 1H), 4.09 (s, 3H), 3.44 (s, 2H),3.39-3.35 (m, 1H), 3.23 (d, J=11.5 Hz, 2H), 3.17-3.11 (m, 3H), 3.07-2.91(m, 3H), 2.78-2.58 (m, 2H), 2.53-2.41 (m, 2H), 2.39 (s, 3H), 1.81 (d,J=10.0 Hz, 2H).

The following examples were prepared according to the procedure used toprepare Example 86.

TABLE 5 Ex. LCMS RT HPLC No. Structure MH⁺ (min) Method 87

450.2 0.713 F 88

434.2 1.018 E 89

448.2 1.019 E 90

434.3 0.94  E 91

420.2 0.95  E 92

420.2 1.12  E 93

448.3 1.21  E 94

420.3 1.12  E 95

448.3 1.21  E 96

402.2 1.27  E 97

421.3 1.22  E 98

437.2 1.08  E 99

464.2 1.38  C

Example 1001-(1-(2-(dimethylamino)acetyl)piperidin-4-yl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1H-benzo[d]imidazol-2(3H)-one

To a solution of5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1-(piperidin-4-yl)-1H-benzo[d]imidazol-2(3H)-one,TFA (0.030 g, 0.061 mmol) and 2-(dimethylamino)acetic acid (0.013 g,0.122 mmol) in DMF (1.00 mL) were added TEA (0.1 mL, 0.717 mmol) andHATU (0.023 g, 0.061 mmol) at room temperature. The mixture was stirredat the same temperature for 16 h. The reaction mass was purified by PrepLCMS using method AB, fractions containing the product were combined anddried using Genevac centrifugal evaporator to afford1-(1-(2-(dimethylamino)acetyl)piperidin-4-yl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1H-benzo[d]imidazol-2(3H)-one(0.0077 g, 0.017 mmol, 27 yield) as a pale solid. LCMS retention time0.759 min [F], MS (ES): m/z=464.3 [M+H]; ¹H NMR (400 MHz, METHANOL-d₄) δppm 8.40 (s, 1H), 8.34 (d, J=1.5 Hz, 1H), 7.25 (s, 1H), 7.13-7.00 (m,2H), 4.77 (d, J=13.6 Hz, 1H), 4.56-4.50 (m, 1H), 4.16 (d, J=14.1 Hz,1H), 4.09 (s, 3H), 3.70 (d, J=14.6 Hz, 1H), 3.57 (d, J=15.1 Hz, 1H),3.32-3.23 (m, 1H), 2.95-2.76 (m, 1H), 2.59-2.49 (m, 7H), 2.47-2.29 (m,4H), 2.01-1.85 (m, 3H).

The following examples were prepared according to the procedure used toprepare Example 100.

TABLE 6 Ex. LCMS RT HPLC No. Structure MH⁺ (min) Method 101

448.3 0.863 E 102

434.3 0.79  E 103

448.3 1.04  E 104

448.3 1.04  E 105

464.2 1.17  C

Example 1067-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-methylpiperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one

Intermediate 106A: tert-butyl4-((2-methyl-6-nitrophenyl)amino)piperidine-1-carboxylate

To a mixture of 2-fluoro-1-methyl-3-nitrobenzene (0.360 g, 2.321 mmol)and tert-butyl 4-aminopiperidine-1-carboxylate (0.558 g, 2.78 mmol) inDMF (10.0 mL) was added K₂CO₃ (0.641 g, 4.64 mmol). The mixture wasstirred at 90° C. for 3 h. The reaction mixture was diluted with water(20 mL), extracted with EtOAc (2×40 mL), the combined extracts werewashed with brine (10 mL), dried under vacuum to afford the crudecompound. The crude material was purified by ISCO using 24 g silicacolumn, the compound was eluted in 20% EA in hexanes, the fractions werecollected and concentrated to afford tert-butyl4-((2-methyl-6-nitrophenyl)amino)piperidine-1-carboxylate (0.540 g,1.610 mmol, 69% yield) as a yellow oil. LCMS retention time 1.52 min[A], MS (ES): m/z=280.2 [M+2H-tBu].

Intermediate 106B: tert-butyl4-((4-bromo-2-methyl-6-nitrophenyl)amino)piperidine-1-carboxylate

To a solution of tert-butyl4-((2-methyl-6-nitrophenyl)amino)piperidine-1-carboxylate (0.450 g,1.342 mmol) in acetonitrile (30.00 mL) was added NBS (0.263 g, 1.476mmol) at 0° C. The mixture was stirred at room temperature for 16 h. Thereaction mass diluted with EtOAc, washed water, dried (Na₂SO₄) andconcentrated to afford crude compound. The crude material was purifiedby ISCO using 24 g silica column, the compound was eluted in 12% EA inhexanes, the fractions were collected and concentrated to affordtert-butyl 4-((4-bromo-2-methyl-6-nitrophenyl)amino)piperidine-1-carboxylate (0.540 g, 1.303 mmol, 97% yield) as a yellowsolid. LCMS retention time 1.75 min [A], MS (ES): m/z=358.4 [M-tBu].

Intermediate 106C: tert-butyl4-((2-methyl-4-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-nitrophenyl)amino)piperidine-1-carboxylate

Mixture of tert-butyl4-((4-bromo-2-methyl-6-nitrophenyl)amino)piperidine-1-carboxylate (0.280g, 0.676 mmol),8-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-[1,2,4]triazolo[1,5-a]pyridine(0.263 g, 1.014 mmol) and potassium phosphate tribasic (0.430 g, 2.028mmol) in dioxane (15.0 mL) and water (5.0 mL) was degassed for 10 min.Next, PdCl₂(dppf)-CH₂Cl₂ adduct (0.055 g, 0.068 mmol) was added, themixture was degassed for 2 min, and then the mixture was stirred at 90°C. for 2 h. The reaction mass was diluted with DCM (20 mL) and water (10mL), the two layers were separated, the aqueous layer was extracted with10% MeOH in DCM (2×30 mL), the combined organic extracts were dried(Na₂SO₄) and concentrated to afford crude compound. The crude materialwas purified by ISCO using 12 g silica column, the compound was elutedin EA, the fractions were collected and concentrated to affordtert-butyl4-((2-methyl-4-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-nitrophenyl)amino)piperidine-1-carboxylate (250 mg, 0.536 mmol, 79% yield) as anoff-white solid. LCMS retention time 1.50 min [A], MS (ES): m/z=465.4[M−H].

Intermediate 106D: tert-butyl4-((2-amino-6-methyl-4-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)phenyl)amino)piperidine-1-carboxylate

To a solution of tert-butyl4-((2-methyl-4-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-nitrophenyl)amino)piperidine-1-carboxylate(0.250 g, 0.536 mmol) in MeOH (10.00 mL) was added Pd—C(0.057 g, 0.536mmol) at room temperature. The mixture was stirred at the sametemperature under a hydrogen bladder for 16 h. The reaction massfiltered through celite, washed with methanol, the filtrate wascollected, concentrated and dried under vacuum to afford tert-butyl4-((2-amino-6-methyl-4-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)phenyl)amino)piperidine-1-carboxylate(210 mg, 0.481 mmol, 90% yield) as a fluffy solid. LCMS retention time1.26 min [A], MS (ES): m/z=437.4 [M+H].

Intermediate 106E: tert-butyl4-(7-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidine-1-carboxylate

To a solution of tert-butyl4-((2-amino-6-methyl-4-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)phenyl)amino)piperidine-1-carboxylate(0.210 g, 0.481 mmol) in acetonitrile (15.00 mL) was added CDI (0.117 g,0.722 mmol) at room temperature. The mixture was stirred at sametemperature for 16 h. The reaction mass was concentrated to afford crudecompound. The crude material was purified by ISCO using 24 g silicacolumn, the compound was eluted in neat EA, the fractions were collectedand concentrated to afford tert-butyl4-(7-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidine-1-carboxylate(150 mg, 0.324 mmol, 67% yield) as a white solid. LCMS retention time1.16 min [A], MS (ES): m/z=463.3 [M+H].

Intermediate 106F:7-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one

To a solution of tert-butyl4-(7-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidine-1-carboxylate(0.150 g, 0.324 mmol) in DCM (5.0 mL) was added TFA (0.50 mL) at 0° C.The mixture was stirred at same temperature for 1 h. Volatiles wereremoved by blowing with nitrogen gas. The mixture was dried under vacuumto afford crude compound. The crude material was triturated with diethylether (2×10 mL), then dried under vacuum to afford7-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one,TFA (0.126 g, 0.265 mmol, 82% yield) as an off-white solid. LCMSretention time 1.350 min [E], MS (ES): m/z=363.2 [M+H]; ¹H NMR (400 MHz,METHANOL-d₄) δ ppm 8.84 (s, 1H), 8.43 (s, 1H), 7.80 (s, 1H), 7.26 (d,J=3.7 Hz, 2H), 3.59 (d, J=12.7 Hz, 2H), 3.29-3.20 (m, 2H), 3.10-2.98 (m,2H), 2.76 (s, 3H), 2.72-2.63 (m, 3H), 2.19 (d, J=12.0 Hz, 2H).

Example 106:7-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-methylpiperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one

To a solution of7-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one,TFA (24 mg, 0.050 mmol) in MeOH (1.5 mL) were added formaldehyde inwater (0.2 mL, 2.178 mmol) and acetic acid (0.2 mL, 3.49 mmol) at roomtemperature. The reaction mixture was stirred for 5 h, then sodiumcyanoborohydride (15.83 mg, 0.252 mmol) was added and the reactionmixture was stirred for another 16 h. The reaction mass was purified byPrep LCMS using method AA, the fractions containing the product werecombined and dried using Genevac centrifugal evaporator to afford7-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-methylpiperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (4.6 mg, 0.012mmol, 23% yield) as a pale solid. LCMS retention time 0.840 min [F], MS(ES): m/z=377.2 [M−H]; ¹H NMR (400 MHz, METHANOL-d₄) δ ppm 8.83 (s, 1H),8.42 (s, 1H), 7.80 (s, 1H), 7.23 (d, J=5.6 Hz, 2H), 4.67-4.53 (m, 1H),3.20 (d, J=11.7 Hz, 2H), 3.03-2.87 (m, 2H), 2.70 (s, 3H), 2.72 (s, 3H),2.56-2.33 (m, 5H), 1.96 (d, J=10.8 Hz, 2H).

The following examples were prepared according to the procedure used toprepare Example 106.

TABLE 7 Ex. LCMS RT HPLC No. Structure MH⁺ (min) Method 107

405.3 0.949 F 108

391.3 0.887 F

Example 109N,N-dimethyl-2-(4-(7-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidin-1-yl)acetamide

To a solution of7-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one,TFA (24 mg, 0.050 mmol) in THF (1.0 mL) and DMF (0.5 mL) solvent mixturewere added 2-chloro-N,N-dimethylacetamide (30.6 mg, 0.252 mmol) and TEA(0.2 mL, 1.435 mmol) at room temperature. The reaction mixture wasstirred at the same temperature for 16 h. The reaction mass was purifiedby Prep LCMS using method AA, the fractions containing the product werecombined and dried using Genevac centrifugal evaporator to afford1-(1-isopropylpiperidin-4-yl)-7-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(5.2 mg, 0.012 mmol, 24% yield) as a pale solid. LCMS retention time1.184 min [E], MS (ES): m/z=448.3 [M+H]; ¹H NMR (400 MHz, METHANOL-d₄) δppm 8.83 (s, 1H), 8.42 (s, 1H), 7.80 (s, 1H), 7.23 (d, J=5.6 Hz, 2H),4.62-4.52 (m, 1H), 3.45 (br. s., 2H), 3.27-3.10 (m, 5H), 3.04-2.89 (m,5H), 2.87 (br. s., 1H), 2.77-2.63 (m, 6H), 2.48 (d, J=10.8 Hz, 3H), 1.91(d, J=11.2 Hz, 2H).

Example 110(R)-1-(1-ethylpiperidin-3-yl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-(trifluoromethyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one

Intermediate 110A: tert-butyl(R)-3-((2-nitro-5-(trifluoromethyl)phenyl)amino)piperidine-1-carboxylate

To a solution of 2-chloro-1-nitro-4-(trifluoromethyl)benzene (300 mg,1.330 mmol) in toluene (20 mL) were added cesium carbonate (1300 mg,3.99 mmol) and BINAP (83 mg, 0.133 mmol). The solution was degassed withnitrogen for 10 min, then palladium (II) acetate (14.93 mg, 0.067 mmol)was added and the mixture was stirred at 110° C. for 16 h. The reactionmixture was diluted with ethyl acetate (50 mL), washed with water (2×30mL), brine (10 mL), dried over sodium sulphate, and concentrated toafford crude product. The crude material was purified by ISCO using 24 gsilica column, the compound eluted with 45% ethyl acetate in petroleumether, the fractions were collected and concentrated to affordtert-butyl (R)-3-((2-nitro-5-(trifluoromethyl)phenyl)amino)piperidine-1-carboxylate (500 mg, 0.706 mmol, 53% yield) as a paleyellow solid. LCMS retention time 3.685 min [B], MS (E⁻) m/z: 334[M−tBu+H].

Intermediate 110B: tert-butyl(R)-3-((4-bromo-2-nitro-5-(trifluoromethyl)phenyl)amino)piperidine-1-carboxylate

tert-butyl(R)-3-((4-bromo-2-nitro-5-(trifluoromethyl)phenyl)amino)piperidine-1-carboxylate(2 g, 4.52 mmol, 82% yield) was prepared according to the generalprocedure described in Intermediate 104B using tert-butyl(R)-3-((2-nitro-5-(trifluoromethyl)phenyl)amino)piperidine-1-carboxylate (700 mg, 1.798 mmol) as a startingintermediate to afford the title compound as a yellow solid. LCMSretention time 4.131 min [B], MS (E⁻) m/z: 466.0 [M−2H].

Intermediate 110C:tert-butyl(R)-3-((4-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-nitro-5-(trifluoromethyl)phenyl)amino)piperidine-1-carboxylate

tert-butyl(R)-3-((4-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-nitro-5-(trifluoromethyl)phenyl)amino)piperidine-1-carboxylate(800 mg, 0.790 mmol, 46% yield) was prepared as according to the generalprocedure described in Intermediate 1B using tert-butyl(R)-3-((4-bromo-2-nitro-5-(trifluoromethyl)phenyl)amino)piperidine-1-carboxylate(800 mg, 1.708 mmol) and8-methoxy-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-[1,2,4]triazolo[1,5-a]pyridine(564 mg, 2.050 mmol) as starting intermediates to afford the titlecompound as a pale yellow solid. LCMS retention time 3.274 min [B], MS(E⁻) m/z: 537.0 [M+H].

Intermediate 110D:tert-butyl(R)-3-((2-amino-4-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-5-(trifluoromethyl)phenyl)amino)piperidine-1-carboxylate

A solution of tert-butyl(R)-3-((4-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-nitro-5-(trifluoromethyl)phenyl)amino)piperidine-1-carboxylate(700 mg, 1.305 mmol) in methanol (20 mL) was purged with nitrogen, thenPd/C (250 mg, 2.349 mmol) was added and the solution was again purgedwith nitrogen. The reaction mixture was stirred at room temperatureunder a hydrogen bladder for 8 h. The reaction mixture was filteredthrough a celite bed, washed with methanol, the filtrate was collectedand concentrated to afford tert-butyl(R)-3-((2-amino-4-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-5-(trifluoromethyl)phenyl)amino)piperidine-1-carboxylate (506 mg, 0.849 mmol, 65% yield) asan orange color solid. LCMS retention time 0.67 min [A], MS (E⁻) m/z:507.4 [M+H].

Intermediate 110E: tert-butyl(R)-3-(5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-oxo-6-(trifluoromethyl)2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidine-1-carboxylate

To a solution of tert-butyl(R)-3-((2-amino-4-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-5-(trifluoromethyl)phenyl)amino)piperidine-1-carboxylate(600 mg, 1.185 mmol) in ACN (60 mL) was added CDI (576 mg, 3.55 mmol) atroom temperature. The reaction mixture was stirred at same temperaturefor 12 h. The reaction mass was concentrated and the residue obtainedwas purified by ISCO using 40 g silica column, compound was eluted with10% methanol in CHCl₃, the fractions were collected and concentrated toafford tert-butyl(R)-3-(5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-oxo-6-(trifluoromethyl)-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidine-1-carboxylate(500 mg, 0.685 mmol, 58% yield) as an off-white solid. LCMS retentiontime 2.691 min [B], MS (E⁻) m/z: 533.1 [M−H].

Intermediate 110F:(R)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(piperidin-3-yl)-6-(trifluoromethyl1,3-dihydro-2H-benzo[d]imidazol-2-one

To a solution of tert-butyl(R)-3-(5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-oxo-6-(trifluoromethyl)-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidine-1-carboxylate(300 mg, 0.563 mmol) in DCM (2 mL) was added TFA (1 mL, 12.98 mmol) atroom temperature. The reaction mixture was stirred at same temperaturefor 1 h. The reaction mass was purged with nitrogen till the removal ofTFA, and dried under vacuum to afford(R)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(piperidin-3-yl)-6-(trifluoromethyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(180 mg, 0.387 mmol, 69% yield) as an off-white solid. LCMS retentiontime 0.972 min [C], MS (E⁻) m/z: 433.1 [M+H]; ¹H NMR (400 MHz, DMSO-d₆)δ 8.54 (d, J=1.0 Hz, 1H), 8.50 (s, 1H), 7.68 (s, 1H), 7.12 (s, 1H), 7.05(s, 1H), 4.38-4.29 (m, 1H), 3.98 (s, 3H), 3.24 (br s, 2H), 3.04-2.95 (m,2H), 2.66-2.55 (m, 1H), 2.36-2.29 (m, 1H), 1.96-1.73 (m, 3H), 1.69-1.56(m, 1H).

Example 110:(R)-1-(1-ethylpiperidin-3-yl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-(trifluoromethyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one

To a solution of(R)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(piperidin-3-yl)-6-(trifluoromethyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(20 mg, 0.046 mmol) in methanol (2 mL) were added acetic acid (0.1 mL,1.747 mmol), acetaldehyde (6.11 mg, 0.139 mmol). The reaction mixturewas stirred at ambient temperature for 30 min, then sodiumcyanoborohydride (14.53 mg, 0.231 mmol) was added and the reactionmixture was further stirred at the same temperature for 3 h. Thereaction mass was concentrated, residue was diluted with water (3 mL)and extracted with ethyl acetate (3×10 mL), dried over sodium sulphate,filtered and concentrated to afford crude compound. The crude sample waspurified by prep LCMS using method AA, the fractions containing theproducts were combined and dried via centrifugal evaporation to afford(R)-1-(1-ethylpiperidin-3-yl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-(trifluoromethyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(15.8 mg, 0.032 mmol, 68% yield). LCMS retention time 1.271 min [E], MS(E⁻) m/z: 461.3 [M+H]; ¹H NMR (400 MHz, DMSO-d₆) δ 11.68-11.56 (m, 1H),8.54 (d, J=1.0 Hz, 1H), 8.51-8.45 (m, 1H), 7.73 (s, 1H), 7.19-7.10 (m,1H), 7.03 (s, 1H), 4.61-4.44 (m, 1H), 3.99 (s, 3H), 3.21-2.81 (m, 3H),2.31-2.18 (m, 1H), 2.00-1.67 (m, 3H), 1.32-1.04 (m, 3H).

The following examples were prepared according to the procedure used toprepare example 110.

TABLE 8 Ex. LCMS RT HPLC No. Structure MH⁺ (min) Method 111

475.2 1.317 C 112

531.3 1.535 C 113

489.2 1.309 C 114

447.2 1.219 C 115

475.2 1.473 C 116

503.2 2.194 C 117

517.2 2.143 C

Example 118(R)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-(2-methoxyethyl)piperidin-3-yl)-6-(trifluoromethyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one

To a stirred solution of(R)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(piperidin-3-yl)-6-(trifluoromethyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(50 mg, 0.116 mmol) in THF (1.5 mL) and DMF (0.5 mL) solvent mixturewere added 1-bromo-2-methoxyethane (48.2 mg, 0.347 mmol) andtriethylamine (0.081 mL, 0.578 mmol) at room temperature. The reactionmixture was stirred at the same temperature for 16 h. The reaction masspurified by Prep LCMS using method AB, the fractions containing theproducts were combined and dried via centrifugal evaporation to afford(R)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-(2-methoxyethyl)piperidin-3-yl)-6-(trifluoromethyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(10.7 mg, 0.022 mmol, 19% yield). LCMS retention time 1.380 min [E], MS(E⁻) m/z: 461.3 [M+H]; ¹H NMR (400 MHz, DMSO-d₆) δ 11.60-11.47 (m, 1H),8.54 (s, 1H), 8.50 (s, 1H), 7.72 (s, 1H), 7.12 (s, 1H), 7.05 (s, 1H),4.50-4.33 (m, 1H), 3.98 (s, 3H), 3.48 (br d, J=4.4 Hz, 2H), 3.24 (s,3H), 3.09-2.70 (m, 4H), 2.65-2.54 (m, 1H), 2.28-2.02 (m, 2H), 1.88-1.75(m, 2H), 1.74-1.59 (m, 1H).

Example 119(S)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-methylpiperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one

Intermediate 119A: 2-fluoro-1-nitro-4-(prop-1-en-2-yl) benzene

To a mixture of 4-bromo-2-fluoro-1-nitrobenzene (5 g, 22.73 mmol) in THF(100 mL) and water (25.00 mL) were added4,4,5,5-tetramethyl-2-(prop-1-en-2-yl)-1,3,2-dioxaborolane (7.64 g, 45.5mmol) and potassium phosphate (14.47 g, 68.2 mmol). The solution wasdegassed for 10 min with argon, PdCl₂(dppf)-CH₂Cl₂ adduct (1.856 g,2.273 mmol) was added and the reaction mixture was heated to 70° C. for12 h. The reaction mixture was diluted with ethyl acetate (150 mL),washed with water (2×100 mL), brine (100 mL), dried over sodiumsulphate, and concentrated to afford crude product. The crude materialwas purified by combiflash using 80 g silica column, the compound waseluted with 20% ethyl acetate in petroleum ether, the fractions werecollected and concentrated to afford2-fluoro-1-nitro-4-(prop-1-en-2-yl)benzene (4 g, 22.08 mmol, 97% yield)as a pale yellow solid. ¹H NMR (400 MHz, DMSO-d₆) δ ppm 8.13 (t, J=8.4Hz, 1H), 7.71 (dd, J=2.0, 13.2 Hz, 1H), 7.62-7.45 (m, 1H), 5.83-5.67 (m,1H), 5.42-5.37 (m, 1H), 2.15 (dd, J=0.7, 1.5 Hz, 3H).

The following Intermediate was prepared according to the procedure usedto prepare Intermediate 119A.

TABLE 9 Intermediate Structure ¹H NMR 119AB

¹H NMR (400 MHz, DMSO-d₆) δ ppm 8.07-8.01 (m, 1H), 7.32-7.24 (m, 2 H),2.78 (q, J = 10 Hz, 2H), 1.29 (t, J = 9.4 Hz, 3H)

Intermediate 119B: 2-fluoro-4-isopropyl-1-nitrobenzene

A solution of 2-fluoro-1-nitro-4-(prop-1-en-2-yl) benzene (4.4 g, 24.29mmol) in dioxane (500 mL) was purged with nitrogen, Pd/C (1.551 g, 14.57mmol) was added, and the mixture was purged with N₂ three times. Theslurry was stirred at room temperature for 12 h under hydrogen bladder.The slurry was filtered through celite; the filtrate was collected andconcentrated to afford 2-fluoro-4-isopropyl-1-nitrobenzene (2.2 g, 12.01mmol, 45% yield) as a pale yellow solid. ¹H NMR (300 MHz, DMSO-d₆) δ ppm8.09 (t, J=8.3 Hz, 1H), 7.51 (dd, J=1.5, 13.0 Hz, 1H), 7.39-7.23 (m,1H), 3.04 (td, J=6.8, 13.8 Hz, 1H), 1.23 (d, J=6.9 Hz, 7H).

Intermediate 119C: tert-butyl (S)-3-((5-isopropyl-2-nitrophenyl)amino)piperidine-1-carboxylate

To a solution of 2-fluoro-4-isopropyl-1-nitrobenzene (1.1 g, 6.00 mmol)in DMF (10 mL) were added (S)-1-Boc-3-aminopiperidine and (2.405 g,12.01 mmol), K₂CO₃ (2.490 g, 18.01 mmol). The reaction mixture wasstirred at 100° C. for 3 h. The reaction mass was concentrated and theresidue obtained was taken in ice cold water, the precipitated whitesolid was filtered and dried under vacuum to afford tert-butyl(S)-3-((5-isopropyl-2-nitrophenyl)amino)piperidine-1-carboxylate (1.5 g,4.13 mmol, 68% yield) as a pale yellow solid. LCMS retention time 3.96min [D], MS (E⁻) m/z: 307 [M−tBu+H].

The following Intermediates were prepared according to the procedureused to prepare Intermediate 119C.

TABLE 10 LCMS RT HPLC Intermediate Structure MH⁺ (min) Method 119CA

364.2 1.252 B 119CB

364.2 2.32  A 119CC

378.3 3.84  B 119CD

323.1 [M − tBu + H] 1.19  A 119CE

308.2 [M − tBu + H] 2.339 B 119CF

348.4 [M − H] 2.18  A

Intermediate 119D: tert-butyl(S)-3-((4-bromo-5-isopropyl-2-nitrophenyl)amino)piperidine-1-carboxylate

To a solution of tert-butyl (S)-3-((5-isopropyl-2-nitrophenyl)amino)piperidine-1-carboxylate (2 g, 5.50 mmol) in ACN (30 mL) was addedNBS (0.979 g, 5.50 mmol) dissolved in ACN (30 mL) at room temperature.The reaction mixture was stirred for 12 h. The reaction mass wasquenched with water (50 ml), extracted with ethyl acetate (3×50 mL),dried over sodium sulphate, filtered and concentrated to afford crudeproduct. The crude material was purified by Combiflash using 40 g silicacolumn, the compound was eluted with 8% EtOAc in petroleum ether, thefractions were collected and concentrated to afford tert-butyl(S)-3-((4-bromo-5-isopropyl-2-nitrophenyl)amino)piperidine-1-carboxylate(2 g, 4.52 mmol, 82% yield) as a yellow solid. LCMS retention time 4.45min [D], MS (E⁻) m/z: 388 [M−tBu+H].

Intermediate 119E:tert-butyl(S)-3-((5-isopropyl-4-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-nitrophenyl)amino)piperidine-1-carboxylate

tert-butyl(S)-3-((5-isopropyl-4-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-nitrophenyl)amino)piperidine-1-carboxylate(2 g, 3.92 mmol, 87% yield) was prepared according to the generalprocedure described in Intermediate 1B, using tert-butyl(S)-3-((4-bromo-5-isopropyl-2-nitrophenyl)amino)piperidine-1-carboxylate (2 g, 4.52 mmol) and8-methoxy-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-[1,2,4]triazolo[1,5-a]pyridine(1.493 g, 5.43 mmol) as starting intermediates to afford the titlecompound as a pale yellow solid. LCMS retention time 3.49 min [D], MS(E⁻) m/z: 511.1 [M+H].

The following Intermediates were prepared according to the procedureused to prepare Intermediate 119E.

TABLE 11 LCMS RT HPLC Intermediate Structure MH⁺ (min) Method 119EA

511.2 3.49  B 119EB

511.4 2.01  A 119EC

525.4 2.32  A 119ED

525.4 3.187 D 119EE

523.4 3.247 D 119EF

497.2 3.272 D 119EG

495.4 3.393 D

Intermediate 119F:tert-butyl(S)-3-((2-amino-5-isopropyl-4-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)phenyl)amino)piperidine-1-carboxylate

tert-Butyl(S)-3-((2-amino-5-isopropyl-4-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)phenyl)amino)piperidine-1-carboxylate(1.1 g, 2.28 mmol, 97% yield) was prepared according to the generalprocedure described in Intermediate 1C, using tert-butyl(S)-3-((5-isopropyl-4-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-nitrophenyl)amino)piperidine-1-carboxylate(1.2 g, 2.350 mmol) as a starting intermediate to afford the titlecompound as a pale yellow solid. LCMS retention time 2.9 min [D], MS(E⁻) m/z: 481.2 [M+H].

Intermediate 119G: tert-butyl(S)-3-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidine-1-carboxylate

tert-Butyl(S)-3-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidine-1-carboxylate(1.1 g, 2.17 mmol, 87% yield) was prepared according to the generalprocedure described in Intermediate 1D, using tert-butyl(S)-3-((2-amino-5-isopropyl-4-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)phenyl)amino)piperidine-1-carboxylate (1.2 g, 2.497 mmol) as a startingintermediate to afford the title compound as an off-white solid. LCMSretention time 2.72 min [D], MS (E⁻) m/z: 505.2 [M−H].

Intermediate 119H:(S)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one

(S)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(0.8 g, 1.94 mmol, 90% yield) was prepared according to the generalprocedure described in Intermediate 1E, using tert-butyl(S)-3-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidine-1-carboxylate(1.1 g, 2.171 mmol) as a starting intermediate to afford the titlecompound as a gummy solid. LCMS retention time 1.56 min [D], MS (E⁻)m/z: 407.2 [M+H].

The following Intermediates were prepared according to the procedureused to prepare Intermediate 119H.

TABLE 12 LCMS RT HPLC Intermediate Structure MH⁺ (min) Method 119HA

407.2 1.43  B 119HB

393.2 1.084 C 119HC

405.3 1.026 D

Example 119:(S)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-methylpiperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one

(S)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-methylpiperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(3.7 mg, 8.71 μmol, 7%) was prepared according to the general proceduredescribed in Example 1 using(S)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(50 mg, 0.123 mmol) as a starting intermediate to afford the titlecompound as a white solid. LCMS retention time 1.33 min [E], MS (E⁻)m/z: 421.2 [M+H]; ¹H NMR (400 MHz, DMSO-d₆) δ ppm 10.88 (s, 1H), 8.46(s, 2H), 7.27 (s, 1H), 6.98 (s, 1H), 6.85 (s, 1H), 4.56 (s, 1H),4.42-4.31 (m, 1H), 3.97-3.96 (m, 1H), 3.99 (s, 2H), 3.03-2.92 (m, 1H),2.84-2.75 (m, 2H), 2.65-2.57 (m, 1H), 2.26 (s, 3H), 2.21-2.12 (m, 1H),2.03-1.93 (m, 1H), 1.92 (s, 1H), 1.83-1.72 (m, 2H), 1.20 (d, J=6.6 Hz,6H).

The following examples were prepared according to the general procedureused to prepare Example 119.

TABLE 13 Ex. LCMS RT HPLC No. Structure MH⁺ (min) Method 120

449.2 1.41  C 121

449.2 1.54  C 122

461.2 1.64  C 123

463.2 1.42  C 124

491.2 1.46  C 125

505.3 1.59  C 126

491.2 1.55  C 127

461.2 1.53  C 128

477.3 1.13  D 129

463.3 1.73  C 130

491.2 2.07  C 131

435.2 1.35  C 132

477.3 1.82  C 133

475.3 1.84  C 134

449.3 1.467 C 135

463.4 0.986 D 136

421.2 1.248 C 137

449.3 1.326 C 138

435.3 1.294 C 139

505.3 1.53  E 140

475.3 1.621 C 141

463.3 1.719 C 142

461.2 1.45  C 143

491.3 1.373 C 144

433.2 1.399 C 145

447.3 1.439 C 146

461.2 1.45  C 147

419.3 1.374 C 148

491.3 2.086 C 149

503.3 1.643 C 150

447.2 1.583 C 151

489.2 2.233 C 152

475.3 2.311 C 153

477.3 2.18  C 154

421.2 0.96  C 155

449.2 1.28  C 156

461.2 1.38  C 157

463.2 1.26  C 158

491.2 1.23  C 159

505.3 1.36  C 160

491.2 1.31  C 161

461.2 1.28  C 162

477.3 1.3  D 163

449.2 1.16  C 164

463.2 1.55  C 165

491.3 1.97  C 166

491.3 1.061 C 167

449.3 1.013 C 168

491.3 1.588 C 169

463.3 1.122 C 170

463.2 1.177 C 171

421.2 1.235 C 172

435.2 1.269 C 173

449.2 1.28  C 174

407.2 1.185 C 175

491.3 1.589 C 176

449.3 1.526 C 177

449.3 1.12  C 178

477.3 1.96  C 179

435.3 1.12  C 180

463.3 1.23  C 181

461.3 1.58  C 182

447.2 1.38  C 183

489.3 1.15  C 184

477.3 1.443 C 185

447.3 1.396 C 186

461.3 1.215 C 187

503.3 1.424 C 188

475.3 1.535 C 189

447.3 1.284 C 190

489.3 2.041 C 191

449.3 1.286 C 192

463.3 1.272 C 193

505.3 1.304 C 194

505.3 1.854 C 195

463.3 1.304 C 196

519.2 1.356 C 197

491.2 1.942 C 198

503.4 1.975 C 199

503.4 1.969 C 200

517.3 1.454 C 201

477.2 1.206 C 202

449.2 1.048 C 203

463.3 1.123 C 204

477.3 1.251 C 205

533.3 2.512 C 206

529.3 1.391 c 207

546.3 1.181 C 208

477.3 1.73  C 209

475.3 1.69  D 210

491.3 1.79  C 211

489.6 1.32  D 212

463.3 0.94  C 213

463.3 1.27  C 214

477.3 0.98  C 215

477.3 0.99  C 216

477.3 1.03  C 217

477.3 1.03  D 218

491.3 1.49  C 219

491.3 1.08  C

Example 220(S)-2-(3-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidin-1-yl)acetamide

To a solution of(S)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(50 mg, 0.123 mmol) in THF (2 mL) and DMF (2 mL) were added TEA (0.08mL, 0.61 mmol) and 2-bromoacetamide (50.9 mg, 0.369 mmol) at roomtemperature. The reaction mixture was then stirred at 50° C. for 12 h.The reaction mass was concentrated, the residue was dissolved methanol,the sample was purified by prep LCMS using method AB, the fractionscontaining the product were combined and dried using Genevac centrifugalevaporator to afford(S)-2-(3-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidin-1-yl)acetamide(2.9 mg, 6.26 μmol, 5%) as a pale yellow solid. LCMS retention time 1.22min [C], MS (E⁻) m/z: 464.2 [M+H]; ¹H NMR (400 MHz, DMSO-d₆) δ ppm 10.87(s, 1H), 8.46 (s, 2H), 7.32 (br d, J=2.2 Hz, 1H), 7.26 (s, 1H), 7.13 (brd, J=1.2 Hz, 1H), 6.98 (s, 1H), 6.85 (s, 1H), 4.50-4.39 (m, 1H), 3.99(s, 3H), 3.04-2.92 (m, 3H), 2.89-2.79 (m, 3H), 2.26-2.13 (m, 2H),1.85-1.70 (m, 3H), 1.20 (d, J=6.8 Hz, 6H).

The following examples were prepared according to the procedure used toprepare example 220.

TABLE 14 Ex. LCMS RT HPLC No. Structure MH⁺ (min) Method 221

465.2 1.41 C 222

513.2 1.36 C 223

465.2 1.27 C 224

513.2 1.27 C 225

463.3 1.507 C 226

465.3 1.39 C 227

451.3 1.454 C

Example 228(R)-1-(1-(dimethylglycyl)piperidin-3-yl)-6-ethyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one

(R)-1-(1-(dimethylglycyl)piperidin-3-yl)-6-ethyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(9.1 mg, 0.019 mmol, 50% yield) was prepared according to the generalprocedure described in Example 100 using(R)-6-ethyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(15 mg, 0.038 mmol) as a starting intermediate to afford title compoundas an off-white solid. LCMS retention time 0.784 min [F], MS (ES):m/z=478.3 [M+H]; ¹H NMR (400 MHz, DMSO-d₆) δ ppm 10.94 (d, J=10.8 Hz,1H), 8.49 (d, J=2.9 Hz, 1H), 8.46 (s, 1H), 7.34 (s, 1H), 7.27 (s, 1H),7.01 (d, J=8.6 Hz, 1H), 6.90 (s, 1H), 4.43 (br. s., 1H), 4.26 (br. s.,1H), 4.15 (br. s., 2H), 4.00 (s, 2H), 3.91 (s, 1H), 3.74 (t, J=11.6 Hz,1H), 2.62 (q, J=7.0 Hz, 2H), 2.38-2.29 (m, 3H), 2.27 (br. s., 2H),1.96-1.77 (m, 3H), 1.65 (br. s., 1H), 1.48 (s, 1H), 1.15-1.02 (m, 3H).

Examples 229 and 2301-(4-(4,4-difluoropiperidin-1-yl)cyclohexyl)-6-isopropyl-5-(8-methoxy-7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one

Intermediate 229A:N-(5-methyl-2-nitrophenyl)-1,4-dioxaspiro[4.5]decan-8-amine:

K₂CO₃ (2.72 g, 19.65 mmol) and 1,4-dioxaspiro[4.5]decan-8-amine (1.236g, 7.86 mmol) were added to a solution of2-fluoro-4-isopropyl-1-nitrobenzene (1.2 g, 6.55 mmol) in DMF (20.0 mL).The mixture was stirred at 110° C. for 14 h. The reaction mixture wasdiluted with ethyl acetate, filtered and washed with excess ethylacetate, the filtrates were collected and concentrated, dried oversodium sulphate and concentrated to afford crude compound. The crudematerial was purified by ISCO using 40 g silica column, the compound waseluted with 25-35% ethyl acetate in petroleum ether, the fractions werecollected and concentrated to affordN-(5-isopropyl-2-nitrophenyl)-1,4-dioxaspiro[4.5]decan-8-amine (1.2 g,3.75 mmol, 57% yield) as a pale yellow solid. LCMS retention time 2.19min [A], MS (ES): m/z=321.1 [M+H].

Intermediate 229B:N-(4-bromo-5-methyl-2-nitrophenyl)-1,4-dioxaspiro[4.5]decan-8-amine

NBS (0.667 g, 3.75 mmol) was added to a solution ofN-(5-isopropyl-2-nitrophenyl)-1,4-dioxaspiro[4.5]decan-8-amine (1.2 g,3.75 mmol) in ACN (20.0 mL) at room temperature. The mixture was stirredat same temperature for 1 h. The reaction mixture was diluted with ethylacetate, filtered and washed with excess ethyl acetate, the combinedorganic layers were washed with water, brine, dried over sodium sulphateand concentrated to afford crude compound. The crude material waspurified by ISCO using 40 g silica column, compound was eluted with25-35% ethyl acetate in pet ether, the fractions were collected andconcentrated to affordN-(4-bromo-5-isopropyl-2-nitrophenyl)-1,4-dioxaspiro[4.5]decan-8-amine(1.1 g, 2.75 mmol, 73% yield) as a light brown solid. LCMS retentiontime 3.074 min [B], MS (ES): m/z=399.1 [M+H].

Intermediate 229C:N-(5-isopropyl-4-(8-methoxy-7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-nitrophenyl)-1,4-dioxaspiro[4.5]decan-8-amine

N-(5-isopropyl-4-(8-methoxy-7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-nitrophenyl)-1,4-dioxaspiro[4.5]decan-8-amine(1.2 g, 2.492 mmol, 90% yield) was prepared according to the generalprocedure described in Intermediate 1B usingN-(4-bromo-5-isopropyl-2-nitrophenyl)-1,4-dioxaspiro[4.5]decan-8-amine(1.1 g, 2.75 mmol) and8-methoxy-7-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-[1,2,4]triazolo[1,5-a]pyridine(1.036 g, 3.58 mmol) as starting intermediates to afford the titlecompound as a pale yellow solid. LCMS retention time 1.98 min [A], MS(ES): m/z=482.3 [M+H].

The following Intermediates were prepared according to the procedureused to prepare Intermediate 229C

TABLE 15 LCMS RT HPLC Intermediate Structure MH⁺ (min) Method 229CA

468.0 2.861 I 229CB

466.2 2.085 A

Intermediate 229D:5-isopropyl-4-(8-methoxy-7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-N1-(1,4-dioxaspiro[4.5]decan-8-yl)benzene-1,2-diamine

To a solution ofN-(5-isopropyl-4-(8-methoxy-7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-nitrophenyl)-1,4-dioxaspiro[4.5]decan-8-amine(1.2 g, 2.492 mmol) in MeOH (30.0 mL) was added Pd/C (0.530 g, 4.98mmol) at room temperature. The reaction mixture was stirred at the sametemperature for 12 h under hydrogen bladder. The reaction mixture wasfiltered through celite, washed with excess methanol and THF, thefiltrates were collected, concentrated and dried under vacuum to afford5-isopropyl-4-(8-methoxy-7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-N1-(1,4-dioxaspiro[4.5]decan-8-yl)benzene-1,2-diamine (950 mg, 2.104 mmol, 84% yield) as an off-whitesolid. LCMS retention time 1.60 min [A], MS (ES): m/z=452.3 [M+H].

Intermediate 229E:6-isopropyl-5-(8-methoxy-7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1,4-dioxaspiro[4.5]decan-8-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one

To a solution of5-isopropyl-4-(8-methoxy-7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-N1-(1,4-dioxaspiro[4.5]decan-8-yl)benzene-1,2-diamine(950 mg, 2.104 mmol) in ACN (30.0 mL) was added CDI (853 mg, 5.26 mmol)at room temperature, stirred at same temperature for 12 h. The reactionmass was concentrated and dried in high vacuum to afford crude material.The crude material was purified by ISCO using 40 g silica column, thecompound was eluted with 8-10% methanol in chloroform, the fractionswere collected and concentrated to afford6-isopropyl-5-(8-methoxy-7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1,4-dioxaspiro[4.5]decan-8-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(800 mg, 1.675 mmol, 80% yield) as a white solid. LCMS retention time1.45 min [A], MS (ES): m/z=476.2 [M−H].

Intermediate 229F:6-isopropyl-5-(8-methoxy-7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(4-oxocyclohexyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one

To a solution of6-isopropyl-5-(8-methoxy-7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1,4-dioxaspiro[4.5]decan-8-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(650 mg, 1.361 mmol) in DCM (10.0 mL) was added TFA (2.62 mL, 34.0 mmol)at 0° C. The reaction mixture was stirred at room temperature for 6 h.The reaction mass was purged with nitrogen, then dried under vacuum toafford6-isopropyl-5-(8-methoxy-7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(4-oxocyclohexyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(550 mg, 1.269 mmol, 93% yield) as an off-white solid. LCMS retentiontime 1.24 min [A], MS (ES): m/z=434.3 [M+H].

Examples 229 and 230:1-(4-(4,4-difluoropiperidin-1-yl)cyclohexyl)-6-isopropyl-5-(8-methoxy-7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one

To a solution of6-isopropyl-5-(8-methoxy-7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(4-oxocyclohexyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(80.0 mg, 0.185 mmol), 4,4-difluoropiperidine (67.1 mg, 0.554 mmol) andacetic acid (1.056 μL, 0.018 mmol) in DMF (1.0 mL), THF (1.5 mL) wasadded. The reaction mixture was stirred at room temperature for 8 h,then sodium cyanoborohydride (23.19 mg, 0.369 mmol) was added at 0° C.and the reaction mixture was stirred at room temperature 16 h. Thereaction mixture was concentrated, purified by prep LCMS using method AAto separate both the isomers, the fractions containing the products werecombined and dried via centrifugal evaporation to separate the isomers.

Example 229: Obtained 3.1 mg as an off-white solid. LCMS retention time1.94 min [E], MS (ES): m/z=539.3 [M+H]; ¹H NMR (400 MHz, DMSO-d₆) δ ppm10.81 (s, 1H), 8.52 (s, 1H), 8.45 (s, 1H), 7.25 (s, 1H), 6.71 (s, 1H),4.27 (s, 3H), 4.21 (br s, 1H), 2.81-2.62 (m, 5H), 2.56 (s, 1H),2.32-2.21 (m, 2H), 2.05-1.85 (m, 10H), 1.84-1.75 (m, 2H), 1.61-1.46 (m,2H), 1.21 (d, J=7.1 Hz, 3H), 1.07 (d, J=6.6 Hz, 3H).

Example 230: Obtained 5 mg as an off-white solid. LCMS retention time2.13 min [E], MS (ES): m/z=539.3 [M+H]; ¹H NMR (400 MHz, DMSO-d₆) δ ppm10.85 (s, 1H), 9.37-9.24 (m, 1H), 8.52 (br s, 1H), 8.46 (s, 1H),7.28-6.94 (m, 2H), 6.73 (s, 1H), 4.43-4.34 (m, 1H), 4.27 (s, 3H), 3.73(br s, 2H), 3.24 (br dd, J=3.1, 4.8 Hz, 1H), 2.98-2.90 (m, 1H), 2.59 (brd, J=7.3 Hz, 1H), 2.44-2.22 (m, 7H), 2.00-1.90 (m, 4H), 1.89-1.73 (m,1H), 1.30-1.13 (m, 5H), 1.09-1.02 (m, 3H).

The following examples were prepared according to the procedure used toprepare Examples 229 and 230.

TABLE 16 Ex. LCMS RT HPLC No. Structure MH⁺ (min) Method 231

475.3 1.36 C 232

475.3 1.612 C 233

504.2 1.449 C 234

504.3 1.169 C 235

531.3 1.48 C 236

531.3 1.737 C 237

491.2 1.536 C 238

491.2 1.858 C 239

531.3 1.167 C 240

531.3 1.751 C 241

545.2 1.782 C 242

545.2 1.782 C 243

504.3 1.169 C 244

551.2 1.291 C 245

551.2 1.482 C 246

525.3 1.74 C 247

525.2 2.011 C 248

531.2 1.791 C 249

531.2 2.068 C 250

507.2 1.578 C 251

507.2 1.933 C 252

253

517.3 1.698 C 254

503.2 1.192 C 257

493.3 1.21 E 258

493.3 1.41 E 259

567.3 1.49 E 260

567.3 1.64 E 261

519.3 1.31 E 262

519.3 1.66 E 263

493.3 1.59 E 264

493.3 1.94 E 265

505.3 1.41 E 266

505.3 1.72 E 267

545.3 1.3 E 268

545.3 1.61 E 269

517.3 1.31 E 270

517.3 1.54 E 271

503.3 1.283 C 272

503.3 1.633 C 273

505.3 1.593 C 274

505.3 2.057 C 275

523.3 1.84 C 276

523.3 2.081 C 277

489.3 1..336 C 278

489.3 1.626 C 279

477.2 1.516 C 280

477.2 1.855 C 281

501.3 1.28 C 282

529.3 1.256 C 283

529.3 1.56 C 284

505.3 1.218 C 285

505.3 1.582 C 286

493.3 1.359 C 287

493.3 1.807 C 288

553.3 1.31 C 289

553.3 1.513 C 290

519.3 1.26 C 291

519.3 1.556 C 292

511.2 1.533 C 293

511.2 1.735 C 294

511.2 1.689 C 295

511.2 1.932 C 296

497.3 1.598 C 297

497.3 1.847 C 298

501.3 1.506 C

Additional examples in the below table were described above in thepreparation of Intermediates.

TABLE 17 Ex. LCMS RT HPLC No. Structure MH⁺ (min) Method 1E

379.2 0.65 E 1EA

363.2 0.705 E 1EB

349.1 0.66 E 1EC

363.2 Check MW 0.89 E 1ED

363.2 Check MW 0.9 E 1EE

377.2 0.932 E 1EF

377.2 0.79 E 1EG

393.2 0.847 E 1EH

379.2 0.72 E 1EI

365.2 0.82 E 106F

363.2 1.15 F 110F

433.1 0.97 C 119F

407.2 1.56 D 119FA

407.2 1.43 B 119FB

393.2 1.1 C 119FC

433.2 1.4 C

Biological Assays

The pharmacological properties of the compounds of this invention may beconfirmed by a number of biological assays. The exemplified biologicalassays, which follow, have been carried out with compounds of theinvention.

TLR7/8/9 Inhibition Reporter Assays

HEK-Blue™-cells (Invivogen) overexpressing human TLR7, TLR8 or TLR9receptors were used for screening inhibitors of these receptors using aninducible SEAP (secreted embryonic alkaline phosphatase) reporter geneunder the control of the IFN-β minimal promoter fused to five NF-κB andAP-1-binding sites. Briefly, cells are seeded into Greiner 384 wellplates (15000 cells per well for TLR7, 20,000 for TLR8 and 25,000 forTLR9) and then treated with test compounds in DMSO to yield a final doseresponse concentration range of 0.05 nM-50 μM. After a 30 minutecompound pre-treatment at room temperature, the cells are thenstimulated with a TLR7 ligand (gardiquimod at a final concentration of7.5 μM), TLR8 ligand (R848 at a final concentration of 15.9 μM) or TLR9ligand (ODN2006 at a final concentration of 5 nM) to activate NF-κB andAP-1 which induce the production of SEAP. After a 22 hour incubation at37° C., 5% CO₂, SEAP levels are determined with the addition ofHEK-Blue™ Detection reagent (Invivogen), a cell culture medium thatallows for detection of SEAP, according to manufacturer'sspecifications. The percent inhibition is determined as the % reductionin the HEK-Blue signal present in wells treated with agonist plus DMSOalone compared to wells treated with a known inhibitor.

TABLE 18 TLR7/8/9 Reporter Assay Data (NT = not tested) TLR7 TLR8 TLR9Ex. IC₅₀ IC₅₀ IC₅₀ No. (nM) (nM) (nM)  1 37.9 54.1 278  2 68.8 107 5564 3 30.5 36.8 4635  4 863 1281 964  5 1548 >3125 2749  6 38.7 46.3 871  741.8 48.6 1331  9 70.8 92.7 638  10 63.2 89.7 354  11 276 143 9546  12144 92.5 7639  13 124 62.9 4421  14 787 155 >50000  15 24.6 22.9 5944 16 17.0 31.4 8948  17 13.1 14.5 5689  18 409 80.8 >50000  19 21.3 32.016367  20 8.86 14.4 3354  21 13.3 13.3 7057  22 4.77 4.08 4628  23 37.730.9 5662  24 12.4 6.74 1576  25 20.2 11.1 4345  26 235 384 6715  2779.5 50.0 8496  28 27.3 22.5 10756  29 211 49.5 >50000  30 8.23 3.124493  31 11.1 1.32 2957  32 20.4 0.61 2337  33 138 10.9 21125  34 20.54.65 3338  35 722 220 >50000  36 171 37.5 30556  37 30.9 28.7 10071  38NT 16.7 5050  39 139 49.3 10573  40 14.8 19.6 6474  41 12.3 27.1 8116 42 26.3 29.5 10536  43 88.5 57.7 16507  44 104 49.0 4719  45 29.5 48.13034  46 172 42.4 7674  47 18.5 32.8 3618  48 14.8 5.33 3774  49 18.23.26 7433  50 38.5 4.86 10868  51 32.5 21.0 8394  52 65.3 25.7 2960  5333.0 35.9 3750  54 29.2 24.0 4233  55 23.1 19.5 5551  56 5.32 11.2 4815 57 8.11 8.87 5936  58 16.2 5.20 4124  59 67.1 18.8 7565  60 27.6 5.746543  61 20.6 2.35 5510  62 12.0 1.85 2346  63 45.1 21.5 10023  64 6.711.76 5487  65 10.5 1.70 3438  66 20.8 0.66 2053  67 33.0 52.0 9620  68414 121 27079  69 96.9 110 19274  70 163 117 17608  71 22.5 147 29046 72 676 249 45791  73 32.4 73.6 8072  74 948 >3125 365  75 1364 14942783  76 1484 251 1709  77 1527 >3125 417  78 1119 1384 2845  79 >31251555 3901  80 >3125 >3125 39639  81 2640 >3125 3882  82 1304 2596 4773 83 2479 1259 5367  84 16.0 9.69 4781  85 21.4 7.14 7945  86 142 3594927  87 497 377 22375  88 333 115 45302  89 111 105 28956  902161 >3125 14628  91 >3125 >3125 >50000  92 820 177 21100  93 565 10512581  94 704 339 >50000  95 117 83.4 14597  96 66.1 45.3 8643  97 38.843.7 19118  98 20.5 60.6 5914  99 391 354 >50000 100 548 175 1659 101173 50.3 2579 102 >3125 >3125 3211 103 215 205 4715 104 71.0 47.6 1447105 399 318 7937 106 29.7 150 3742 107 32.9 249 2988 108 11.5 83.1 1163109 74.1 541 14309 110 16.8 4.06 7819 111 23.6 12.6 9937 112 30.8 20.312697 113 488 113 >50000 114 2.87 0.29 618 115 34.1 14.4 13404 116 44.157.8 34192 117 64.4 33.3 11773 118 26.5 22.7 18061 119 31.8 2.37 26283120 0.64 0.80 1941 121 28.6 1.82 13568 122 15.1 1.50 12725 123 1255.56 >50000 124 63.8 4.33 20791 125 34.1 2.37 7721 126 81.8 3.64 27763127 14.3 2.80 15641 128 44.0 2.63 >50000 129 12.8 4.00 3687 130 31.18.52 9614 131 26.8 17.2 28328 132 18.3 10.1 10957 133 17.3 5.90 7139 1341.98 5.93 9332 135 26.3 20.0 >50000 136 2.18 2.01 14944 137 0.74 1.377070 138 2.73 2.64 17885 139 0.76 1.27 7806 140 1.30 3.92 6459 141 0.120.56 3881 142 0.64 2.20 6020 143 3.35 3.24 10234 144 8.58 5.02 14124 1453.70 2.10 14334 146 182 6.05 >50000 147 66.9 23.5 >50000 148 0.49 1.099614 149 3.97 4.58 15749 150 5.52 4.25 11935 151 11.0 21.7 17675 1525.55 24.5 NT 153 0.58 2.27 13080 154 2.12 1.52 23545 155 6.33 9.56 11877156 17.9 4.77 23828 157 76.8 5.42 >50000 158 11.2 16.2 21389 159 7.234.52 7250 160 8.66 5.62 14282 161 7.28 6.04 11320 162 73.0 6.56 >50000163 7.49 7.58 15327 164 12.3 9.67 17168 165 10.9 7.03 8720 166 1.90 0.5414930 167 3.08 0.82 16562 168 5.45 1.53 15155 169 1.84 0.74 18307 1706.25 1.27 19979 171 4.56 3.03 10738 172 1.45 1.75 6831 173 32.018.0 >50000 174 1.14 1.39 7345 175 0.83 2.23 7387 176 3.38 8.00 NT 1771.07 4.34 10698 178 0.81 2.62 7469 179 1.06 2.48 6857 180 1.42 4.2910258 181 0.81 1.68 6773 182 1.93 2.31 7942 183 12.2 6.44 33480 184 12.114.3 26648 185 3.39 0.36 7074 186 0.95 0.13 5987 187 4.09 0.80 12793 1887.14 0.95 22173 189 9.82 3.11 >50000 190 5.72 0.08 5045 191 1.49 0.5811660 192 1.97 0.44 16552 193 2.22 0.48 21366 194 2.28 0.11 2079 1951.39 0.27 13877 196 4.10 0.05 8962 197 0.80 0.04 6260 198 4.92 0.15 2128199 5.03 0.53 3366 200 9.02 0.13 7051 201 2.07 1.54 22861 202 3.51 0.8122993 203 4.72 1.34 30947 204 3.21 1.23 11725 205 4.76 1.63 11585 2061.30 0.57 6534 207 23.9 4.15 4631 208 6.52 3.77 3317 209 7.96 20.4 12705210 2.86 3.30 2361 211 0.05 0.05 2979 212 25.4 4.40 >50000 213 37.34.62 >50000 214 17.1 19.3 NT 215 13.4 13.7 21010 216 14.6 26.4 >50000217 11.2 5.40 >50000 218 5.33 5.19 24185 219 0.05 0.15 25091 220 244100 >50000 221 11.3 5.67 20578 222 138 53.2 >50000 223 16.9 9.01 13240224 82.4 25.5 >50000 225 7.96 3.37 33768 226 1.13 4.15 14191 227 2.864.42 15207 228 34.9 38.7 14118 229 7.31 2.18 30002 230 60.3 5.49 >50000231 1.68 0.81 15101 232 1.40 0.44 7782 233 11.0 1.90 >50000 234 42.710.5 >50000 235 1.52 0.39 11161 236 3.54 0.35 2590 237 1.31 0.33 11291238 0.81 0.26 8089 239 1.69 0.21 13021 240 3.52 0.13 4426 241 3.010.49 >50000 242 10.4 1.12 23725 243 119 81.5 >50000 244 8.30 3.54 NT 2455.96 11.7 17281 246 2.81 0.16 15513 247 30.2 0.70 14891 248 1.12 0.179773 249 0.50 0.08 1997 250 1.99 0.36 7247 251 3.54 0.95 11880 252 40.524.8 >50000 253 4.75 4.33 11129 254 6.81 3.38 14107 257 6.97 1.38 23305258 4.25 0.60 24341 259 10.4 1.85 40451 260 41.5 0.38 6356 261 15.5 2.2318727 262 2.30 0.68 15503 263 7.93 2.91 19688 264 28.4 5.93 17528 2657.18 2.72 19093 266 13.4 4.47 23021 267 2.10 0.12 >50000 268 15.8 1.0817390 269 5.73 1.58 25619 270 19.3 2.83 11615 271 6.06 0.36 8165 2725.37 0.49 6753 273 9.22 0.87 13505 274 6.78 1.09 16793 275 13.7 0.8119851 276 61.7 1.92 15338 277 2.39 0.74 7383 278 7.88 1.57 15250 2792.89 1.52 10789 280 4.91 2.75 20570 281 12.4 2.67 13069 282 10.1 0.5114376 283 1.82 0.09 5337 284 0.70 0.18 3560 285 0.66 0.13 8306 286 0.700.90 4284 287 1.53 1.66 10858 288 5.09 0.75 47771 289 11.9 4.44 >50000290 1.38 0.53 7095 291 1.71 1.86 12308 292 2.21 0.13 28943 293 10.9 7.7423360 294 1.20 3.14 35185 295 41.8 7.90 22179 296 31.4 3.40 >50000 29737.1 8.40 16165 298 16.5 3.76 3794 1 E 366 225 2640 1 EA 344 439 5455 1EB 1160 1029 347 1 EC 105 22.5 381 1 ED 18.1 38.1 524 1 EE 19.3 31.82157 1 EF 40.7 33.2 2305 1 EG 53.2 32.6 3655 1 EH 43.0 49.6 809 1EI >3125 >3125 1183 106 F 50.5 433 1024 110 F 28.2 14.8 2706 119 FB 5.476.99 2497 119 FC 3.26 7.17 11698 — — — —

What is claimed is:
 1. A compound of Formula (I)

or a salt thereof, wherein: G is:

(iv) a 9-membered heterocyclic ring selected from:

or (v) 10-membered heterocyclic ring selected from:

each R₁ is independently hydrogen, F, Cl, —CN, C₁₋₃ alkyl, C₁₋₂fluoroalkyl, —OCH₃, or —S(O)₂(C₁₋₃ alkyl); each R₂ is independentlyhalo, —CN, —OH, —NO₂, C₁₋₄ alkyl, C₁₋₂ fluoroalkyl, C₁₋₂ cyanoalkyl,C₁₋₃ hydroxyalkyl, C₁₋₃ aminoalkyl, —O(CH₂)₁₋₂OH, —(CH₂)₀₋₄O(C₁₋₄alkyl), C₁₋₃ fluoroalkoxy, —O(CH₂)₁₋₂OC(O)(C₁₋₃ alkyl),—O(CH₂)₁₋₂NR_(x)R_(x), —C(O)O(C₁₋₃ alkyl), —(CH₂)₀₋₂C(O)NR_(y)R_(y),—C(O)NR_(x)(C₁₋₅ hydroxyalkyl), —C(O)NR_(x)(C₂₋₆ alkoxyalkyl),—C(O)NR_(x)(C₃₋₆ cycloalkyl), —NR_(y)R_(y), —NR_(y)(C₁₋₃ fluoroalkyl),—NR_(y)(C₁₋₄ hydroxyalkyl), —NR_(x)CH₂(phenyl), —NR_(x)S(O)₂(C₃₋₆cycloalkyl), —NR_(x)C(O)(C₁₋₃ alkyl), —NR_(x)CH₂(C₃₋₆ cycloalkyl),—(CH₂)₀₋₂S(O)₂(C₁₋₃ alkyl), —(CH₂)₀₋₂(C₃₋₆ cycloalkyl),—(CH₂)₀₋₂(phenyl), morpholinyl, dioxothiomorpholinyl, dimethylpyrazolyl, methylpiperidinyl, methylpiperazinyl, amino-oxadiazolyl,imidazolyl, pyrimidinyl, triazolyl, or —C(O)(thiazolyl); R_(2a) is C₁₋₆alkyl, C₁₋₃ fluoroalkyl, C₁₋₆ hydroxyalkyl, C₁₋₃ aminoalkyl,—(CH₂)₀₋₄O(C₁₋₃ alkyl), C₃₋₆ cycloalkyl, —(CH₂)₁₋₃C(O)NR_(y)R_(y),—CH₂(C₃₋₆ cycloalkyl), —CH₂(phenyl), tetrahydrofuranyl,tetrahydropyranyl, or phenyl; each R_(2b) is independently hydrogen,halo, —CN, —NR_(x)R_(x), C₁₋₆ alkyl, C₁₋₃ fluoroalkyl, C₁₋₃hydroxyalkyl, C₁₋₃ fluoroalkoxy, —(CH₂)₀₋₂O(C₁₋₃ alkyl),—(CH₂)₀₋₃C(O)NR_(x)R_(x), —(CH₂)₁₋₃(C₃₋₆ cycloalkyl), —C(O)O(C₁₋₃alkyl), —C(O)NR_(x)(C₁₋₃ alkyl), —CR_(x)═CR_(x)R_(x), or —CR_(x)═CH(C₃₋₆cycloalkyl); R_(2c) is R_(2a) or R_(2b); R_(2d) is R_(2a) or R_(2b);provided that one of R_(2c) and R_(2d) is R_(2a), and the other ofR_(2c) and R₂ is R_(2b); A is: (i) hydrogen, —NR_(y)R_(y), or—OCH₂CH₂NR_(y)R_(y); (ii) —CR_(x)R_(x)R₃, —CH₂CH₂NR_(x)R₃,—C(O)NR_(x)R₃, —NR_(x)R₃, —NR_(x)CH₂CH₂R₃, —OR₃, or —NR_(x)C(O)R₃; or(iii) R₃; R₃ is C₃₋₆ cycloalkyl, azetidinyl, morpholinyl, piperazinyl,piperidinyl, or pyrrolidinyl, each substituted with zero to 2 R_(3a);each R_(3a) is independently C₁₋₆ alkyl, C₁₋₆ cyanoalkyl, C₁₋₆fluoroalkyl, C₁₋₆ hydroxyalkyl, C₂₋₆ alkoxyalkyl, —CH₂C(O)NR_(y)R_(y),—C(O)(CH₂)₁₋₃NR_(y)R_(y), —NR_(y)R_(y), —NR_(y)(C₁₋₃ fluoroalkyl),—NR_(y)(C₂₋₄ alkoxyalkyl), —(CH₂)₁₋₃S(O)₂(C₁₋₃ alkyl), —(CH₂)₁₋₃NR_(x)S(O)₂(C₁₋₃ alkyl), —NR_(x)(CH₂)₁₋₂C(O)NR_(y)R_(y),—NR_(x)(CH₂)₁₋₃S(O)₂(C₁₋₃ alkyl), —NR_(x)R_(w), —NR_(x)CH₂R_(w), R_(w),—CH₂R_(w), oxaazaspiro[3.3]heptanyl, dioxothiaazaspiro[3.3]heptanyl,oxaazabicyclo[3.2.1]octanyl, oxaazaspiro[3.4]octanyl, oroxaazaspiro[3.5]nonanyl; R_(w) is C₃₋₆ cycloalkyl, azetidinyl,pyrrolidinyl, oxetanyl, tetrahydrofuranyl, tetrahydropyranyl,piperidinyl, morpholinyl, piperazinonyl, oxazepanyl, thiomorpholinyl,pyridinyl, pyrimidinyl, or triazolyl, each substituted with zero to 3substituents selected from F, Cl, —OH, —CN, C₁₋₃ alkyl, C₁₋₃hydroxyalkyl, C₁₋₃ fluoroalkyl, C₁₋₃ alkoxy —CH₂OCH₃, and —S(O)₂CH₃;each R_(x) is independently hydrogen or —CH₃; each R_(y) isindependently hydrogen or C₁₋₆ alkyl; n is zero, 1, or 2; and p is zero,1, or
 2. 2. The compound according to claim 1 having the structure ofFormula (II)

or a salt thereof, wherein: each R₁ is independently hydrogen, C₁₋₃alkyl, or —CF₃; each R₂ is independently hydrogen, —CH₃, or —OCH₃; A iscyclohexyl or piperidinyl, each substituted with zero to 2 R_(3a); eachR_(3a) is independently C₁₋₆ alkyl, C₁₋₂ cyanoalkyl, C₁₋₄ fluoroalkyl,C₂₋₄ alkoxyalkyl, —(CH₂)₁₋₃S(O)₂(C₁₋₃ alkyl), —CH₂(C₃₋₆ cycloalkyl),—CH₂R_(w), —CH₂C(O)NR_(x)R_(x), —NR_(y)R_(y), —NR_(x)(C₁₋₃ fluoroalkyl),—NR_(x)(C₂₋₄ alkoxyalkyl), —NR_(x)R_(w), —NR_(x)CH₂R_(w), R_(w),oxaazaspiro[3.3]heptanyl, dioxothiaazaspiro[3.3]heptanyl,oxaazabicyclo[3.2.1]octanyl, or oxaazaspiro[3.5]nonanyl; R_(w) is C₃₋₆cycloalkyl, azetidinyl, pyrrolidinyl, oxetanyl, tetrahydrofuranyl,tetrahydropyranyl, piperidinyl, piperazinonyl, oxazepanyl,thiomorpholinyl, pyridinyl, pyrimidinyl, or triazolyl, each substitutedwith zero to 2 substituents selected from F, —OH, C₁₋₃ alkyl, —CF₃,—OCH₃, —CH₂OCH₃, and —S(O)₂CH₃; each R_(x) is independently hydrogen or—CH₃; each R_(y) is independently hydrogen or C₁₋₆ alkyl; n is zero, 1,or 2; and p is zero, 1, or
 2. 3. The compound according claim 1 or asalt thereof, wherein: A is cyclohexyl or piperidinyl, each substitutedwith zero to 2 R_(3a); and each R_(3a) is independently C₁₋₆ alkyl,—CH₂CN, C₃₋₄ fluoroalkyl, —(CH₂)₁₋₂OCH₃, —(CH₂)₁₋₂S(O)₂(C₁₋₃ alkyl),—CH₂(C₃₋₆ cycloalkyl), —CH₂R_(w), —CH₂C(O)NR_(x)R_(x), —NR_(y)R_(y),—NR_(x)(C₁₋₃ fluoroalkyl), —NH(C₂₋₃ alkoxyalkyl), —NR_(x)R_(w),—NR_(x)CH₂R_(w), R_(w), oxaazaspiro[3.3]heptanyl,dioxothiaazaspiro[3.3]heptanyl, oxaazabicyclo[3.2.1]octanyl, oroxaazaspiro[3.5]nonanyl.
 4. The compound according to claim 1 or a saltthereof, wherein: A is cyclohexyl or piperidinyl, each substituted withzero to 1 R_(3a); each R_(3a) is independently —CH₃, —CH₂CH₃,—CH₂CH₂CH₃, —CH(CH₃)₂, —CH₂CH(CH₃)₂, —CH₂C(CH₃)₃, —CH(CH₃)CH₂CH₃,—CH₂CH₂CH(CH₃)₂, —CH(CH₂CH₃)₂, —CH₂CH(CH₂CH₃)₂, —CH₂CH₂C(CH₃)₃, —CH₂CN,—CH₂CH₂CF₃, —CH₂CH₂CH₂CF₃, —CH₂CH₂OCH₃, —CH₂CH₂S(O)₂CH₃, —CH₂(C₃₋₅cycloalkyl), —CH₂(pyridinyl), —CH₂(methoxypyrimidinyl),—CH₂(tetrahydrofuranyl), —CH₂(tetrahydropyranyl), —CH₂(methyltriazolyl),—CH₂C(O)NH₂, —CH₂C(O)NH(CH₃), —C(O)CH₂N(CH₃)₂, —NH₂, —NH(CH₂CH₃),—NH(CH₂CH₂CH₃), —NH(CH(CH₃)₂), —NH(CH₂CH(CH₃)₂), —NH(CH(CH₃)CH₂CH₃),—NH(CH₂C(CH₃)₃), —NH(CH₂CH(CH₂CH₃)₂), —NH(CH₂CH₂CF₃), —NH(CH₂CH₂OCH₃),—N(CH₃)₂, —N(CH₃)(CH(CH₃)₂)), —N(CH₃)(CH₂CH₂CF₃), —N(CH₂CH₃)₂,—N(CH₂CH₂CH₃)₂, —N(CH₂CH(CH₃)₂)₂, —NH(C₃₋₆ cycloalkyl), —NH(oxetanyl),—NH(tetrahydropyranyl), —NH(isopropylpiperidinyl),—N(CH₃)(tetrahydropyranyl), —N(CH₃)(cyclohexyl), —NH(CH₂(cyclopropyl)),—NH(CH₂(cyclohexyl)), —NH(CH₂(methylsulfonylcyclopropyl)),—NH(CH₂(tetrahydropyranyl)), —NH(CH₂(methyltriazolyl)),fluoroazetidinyl, difluoroazetidinyl, methoxyazetidinyl,hydroxy,trifluoromethylazetidinyl, cyclobutyl, oxetanyl,tetrahydrofuranyl, pyrrolidinyl, difluoropyrrolidinyl,tetrahydropyranyl, thiomorpholinyl, fluoropiperidinyl,difluoropiperidinyl, methoxypiperidinyl, methoxymethylpiperidinyl,methylsulfonylpiperidinyl, piperazinonyl, oxazepanyl,oxaazaspiro[3.3]heptanyl, dioxothiaazaspiro[3.3]heptanyl,oxaazabicyclo[3.2.1]octanyl, or oxaazaspiro[3.5]nonanyl.
 5. The compoundaccording to claim 1 having the structure of Formula (III):


6. The compound according to claim 1 or a salt thereof, wherein: A iscyclohexyl substituted with zero to 2 R_(3a).
 7. The compound accordingto claim 1 or a salt thereof, wherein: A is piperidinyl substituted withzero to 2 R_(3a).
 8. (canceled)
 9. A pharmaceutical compositioncomprising a compound according to claim 1 or apharmaceutically-acceptable salt thereof; and a pharmaceuticallyacceptable carrier.
 10. (canceled)
 11. (canceled)
 12. The compoundaccording to claim 1 or a salt thereof, wherein: A is hydrogen,—NR_(y)R_(y), or —OCH₂CH₂NR_(y)R_(y).
 13. The compound according toclaim 1 or a salt thereof, wherein: A is —CR_(x)R_(x)R₃,—CH₂CH₂NR_(x)R₃, —C(O)NR_(x)R₃, —NR_(x)R₃, —NR_(x)CH₂CH₂R₃, —OR₃, or—NR_(x)C(O)R₃.
 14. The compound according to claim 1 or a salt thereof,wherein: A is C₃₋₆ cycloalkyl, azetidinyl, morpholinyl, piperazinyl,piperidinyl, or pyrrolidinyl, each substituted with zero to 2 Ria. 15.The compound according to claim 1 or a salt thereof, wherein saidcompound is:5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1-(1-methylpiperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(1);1-(1-isopropylpiperidin-4-yl)-6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(2);6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-methylpiperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(3);5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-methylpiperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(4);1-(1-isopropylpiperidin-4-yl)-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(5);1-(1-ethylpiperidin-4-yl)-6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(6);6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-propylpiperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(7);1-(1-ethylpiperidin-4-yl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1,3-dihydro-2H-benzo[d]imidazol-2-one(9);1-(1-isopropylpiperidin-4-yl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1,3-dihydro-2H-benzo[d]imidazol-2-one(10);(S)-6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-methylpiperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(11);(S)-1-(1-ethylpiperidin-3-yl)-6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(12);(S)-1-(1-isopropylpiperidin-3-yl)-6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(13);(S)-6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-(oxetan-3-yl)piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (14);(R)-6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-methylpiperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(15);(R)-1-(1-ethylpiperidin-3-yl)-6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(16);(R)-1-(1-isopropylpiperidin-3-yl)-6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(17);(R)-6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-(oxetan-3-yl)piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (18);1-((1s,4s)-4-(dimethylamino)cyclohexyl)-6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(19);1-((1s,4s)-4-(diethylamino)cyclohexyl)-6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(20);1-((1s,4s)-4-(ethylamino)cyclohexyl)-6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(21);1-((1s,4s)-4-(isopropylamino)cyclohexyl)-6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(22);1-((1r,4r)-4-(dimethylamino)cyclohexyl)-6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(23);1-((1r,4r)-4-(ethylamino)cyclohexyl)-6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(24);1-((1r,4r)-4-(isopropylamino)cyclohexyl)-6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(25);(R)-6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-neopentylpiperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(26);(R)-6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-(tetrahydro-2H-pyran-4-yl)piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(27);1-((3R)-1-(sec-butyl)piperidin-3-yl)-6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(28);(R)-6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-(3,3,3-trifluoropropyl)piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(29);6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-((1s,4s)-4-((tetrahydro-2H-pyran-4-yl)amino)cyclohexyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(30);6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-((1s,4s)-4-(3,3,3-trifluoropropyl)amino)cyclohexyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(31);6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-((1s,4s)-4-(neopentylamino)cyclohexyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(32);6-methyl-1-((1s,4s)-4-(((1-methyl-1H-1,2,4-triazol-3-yl)methyl)amino)cyclohexyl)-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(33);1-((1s,4s)-4-(sec-butylamino)cyclohexyl)-6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(34);(R)-6-methyl-1-(1-((1-methyl-1H-1,2,4-triazol-3-yl)methyl)piperidin-3-yl)-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(35);(S)-1-(1-((2-methoxypyrimidin-5-yl)methyl)piperidin-3-yl)-6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(36);(R)-1-(1-(cyclopropylmethyl)piperidin-3-yl)-6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(37);(R)-1-(1-isopentylpiperidin-3-yl)-6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(38);(R)-6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-(4,4,4-trifluorobutyl)piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(39);(R)-1-(1-isobutylpiperidin-3-yl)-6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(40);(R)-6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-((tetrahydro-2H-pyran-4-yl)methyl)piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(41);(R)-6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-propylpiperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(42);6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-((3R)-1-((tetrahydrofuran-3-yl)methyl)piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(43);(R)-1-(1-(3,3-dimethylbutyl)piperidin-3-yl)-6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(44);(R)-1-(1-(2-ethylbutyl)piperidin-3-yl)-6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(45);(R)-6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-(pyridin-3-ylmethyl)piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(46);(R)-1-(1-(cyclopentylmethyl)piperidin-3-yl)-6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(47);1-((1s,4s)-4-(dimethylamino)cyclohexyl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1,3-dihydro-2H-benzo[d]imidazol-2-one(48);5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1-((1s,4s)-4-((tetrahydro-2H-pyran-4-yl)amino)cyclohexyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(49);1-((1s,4s)-4-(isopropylamino)cyclohexyl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1,3-dihydro-2H-benzo[d]imidazol-2-one(50);(R)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1-(1-methylpiperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(51);(R)-1-(1-ethylpiperidin-3-yl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1,3-dihydro-2H-benzo[d]imidazol-2-one(52);(R)-1-(1-isopropylpiperidin-3-yl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1,3-dihydro-2H-benzo[d]imidazol-2-one(53);(R)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1-(1-propylpiperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(54);(R)-1-(1-(cyclopropylmethyl)piperidin-3-yl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1,3-dihydro-2H-benzo[d]imidazol-2-one(55);(R)-1-(1-isobutylpiperidin-3-yl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1,3-dihydro-2H-benzo[d]imidazol-2-one(56);(R)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1-(1-((tetrahydro-2H-pyran-4-yl)methyl)piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(57);1-((1s,4s)-4-(cyclobutylamino)cyclohexyl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1,3-dihydro-2H-benzo[d]imidazol-2-one(58);5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1-((1s,4s)-4-(oxetan-3-ylamino)cyclohexyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(59);1-((1s,4s)-4-((cyclopropylmethyl)amino)cyclohexyl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1,3-dihydro-2H-benzo[d]imidazol-2-one(60);1-((1s,4s)-4-(isobutylamino)cyclohexyl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1,3-dihydro-2H-benzo[d]imidazol-2-one(61);1-((1s,4s)-4-(cyclohexylamino)cyclohexyl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1,3-dihydro-2H-benzo[d]imidazol-2-one(62);1-((1s,4s)-4-(ethylamino)cyclohexyl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1,3-dihydro-2H-benzo[d]imidazol-2-one(63);5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1-((1s,4s)-4-(propylamino)cyclohexyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (64);1-((1s,4s)-4-(cyclopentylamino)cyclohexyl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1,3-dihydro-2H-benzo[d]imidazol-2-one(65);1-((1s,4s)-4-((cyclohexylmethyl)amino)cyclohexyl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1,3-dihydro-2H-benzo[d]imidazol-2-one(66);(R)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1-(1-(pentan-3-yl)piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (67);(R)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1-(1-(3,3,3-trifluoropropyl)piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(68);(R)-1-(1-cyclobutylpiperidin-3-yl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1,3-dihydro-2H-benzo[d]imidazol-2-one(69);(R)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1-(1-(tetrahydro-2H-pyran-4-yl)piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(70);(R)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1-(1-neopentylpiperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(71);(R)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1-(1-(oxetan-3-yl)piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (72);(R)-1-(1-(2-ethylbutyl)piperidin-3-yl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1,3-dihydro-2H-benzo[d]imidazol-2-one(73);5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-methylpiperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(74);1-(1-(2-ethylbutyl)piperidin-4-yl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(75);5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-propylpiperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(76);1-(1-isopropylpiperidin-4-yl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(77);5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-((tetrahydro-2H-pyran-4-yl)methyl)piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (78);1-(1-(cyclopropylmethyl)piperidin-4-yl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(79);5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-(oxetan-3-yl)piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(80);5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-(tetrahydrofuran-3-yl)piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (81);5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-((tetrahydrofuran-3-yl)methyl)piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (82);1-(1-cyclobutylpiperidin-4-yl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(83);1-((1s,4s)-4-(isopropyl(methyl)amino)cyclohexyl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1,3-dihydro-2H-benzo[d]imidazol-2-one(84);5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1-((1s,4s)-4-(methyl(tetrahydro-2H-pyran-4-yl)amino)cyclohexyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(85);2-(4-(5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidin-1-yl)-N,N-dimethylacetamide(86);2-(4-(5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidin-1-yl)-N-methylacetamide(87);N-methyl-2-(4-(6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidin-1-yl)acetamide(88);N,N-dimethyl-2-(4-(6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidin-1-yl)acetamide(89);N,N-dimethyl-2-(4-(5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidin-1-yl)acetamide(90);N,N-dimethyl-2-(4-(6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidin-1-yl)acetamide(91);(S)-2-(3-(6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidin-1-yl)acetamide(92);(S)—N,N-dimethyl-2-(3-(6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidin-1-yl)acetamide(93);(R)-2-(3-(6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidin-1-yl)acetamide(94);(R)—N,N-dimethyl-2-(3-(6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidin-1-yl)acetamide(95);(R)-2-(3-(6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidin-1-yl)acetonitrile(96);(R)-1-(1-(2-methoxyethyl)piperidin-3-yl)-6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(97);(R)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-(2-methoxyethyl)piperidin-3-yl)-6-methyl-1,3-dihydro-2H-benzo[d]imidazol-2-one(98);(R)-2-(3-(5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidin-1-yl)-N,N-dimethylacetamide(99);1-(1-(2-(dimethylamino)acetyl)piperidin-4-yl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1H-benzo[d]imidazol-2(3H)-one(100);1-(1-(dimethylglycyl)piperidin-4-yl)-6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(101);1-(1-(dimethylglycyl)piperidin-4-yl)-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(102);(S)-1-(1-(dimethylglycyl)piperidin-3-yl)-6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(103);(R)-1-(1-(dimethylglycyl)piperidin-3-yl)-6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(104);1-(1-(dimethylglycyl)piperidin-3-yl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1,3-dihydro-2H-benzo[d]imidazol-2-one(105);7-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-methylpiperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(106);1-(1-isopropylpiperidin-4-yl)-7-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(107);1-(1-ethylpiperidin-4-yl)-7-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(108);N,N-dimethyl-2-(4-(7-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidin-1-yl)acetamide(109);(R)-1-(1-ethylpiperidin-3-yl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-(trifluoromethyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(110);(R)-1-(1-isopropylpiperidin-3-yl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-(trifluoromethyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(111);(R)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-((tetrahydro-2H-pyran-4-yl)methyl)piperidin-3-yl)-6-(trifluoromethyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(112);(R)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-(oxetan-3-yl)piperidin-3-yl)-6-(trifluoromethyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(113);(R)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-methylpiperidin-3-yl)-6-(trifluoromethyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(114);(R)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-propylpiperidin-3-yl)-6-(trifluoromethyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(115);(R)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-neopentylpiperidin-3-yl)-6-(trifluoromethyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(116);(R)-1-(1-(2-ethylbutyl)piperidin-3-yl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-(trifluoromethyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(117);(R)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-(2-methoxyethyl)piperidin-3-yl)-6-(trifluoromethyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(118);(S)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-methylpiperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(119);(S)-6-isopropyl-1-(1-isopropylpiperidin-3-yl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(120);(S)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-propylpiperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(121);(S)-1-(1-cyclobutylpiperidin-3-yl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(122);(S)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-(oxetan-3-yl)piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (123);(S)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-(tetrahydro-2H-pyran-4-yl)piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(124);(S)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-((tetrahydro-2H-pyran-4-yl)methyl)piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(125);6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-((3S)-1-((tetrahydrofuran-3-yl)methyl)piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(126);(S)-1-(1-(cyclopropylmethyl)piperidin-3-yl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(127);(S)-1-(1-(cyclopropylmethyl)piperidin-3-yl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(128);(S)-1-(1-isobutylpiperidin-3-yl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(129);(S)-1-(1-(2-ethylbutyl)piperidin-3-yl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(130);(S)-1-(1-isopentylpiperidin-3-yl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(131);(S)-1-(1-isopentylpiperidin-3-yl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(132);(S)-1-(1-(cyclobutylmethyl)piperidin-3-yl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(133);(R)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-propylpiperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(134);(R)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-(oxetan-3-yl)piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (135);(R)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-methylpiperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(136);(R)-6-isopropyl-1-(1-isopropylpiperidin-3-yl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(137);(R)-1-(1-ethylpiperidin-3-yl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(138);(R)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-((tetrahydro-2H-pyran-4-yl)methyl)piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(139);(R)-1-(1-(cyclobutylmethyl)piperidin-3-yl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(140);(R)-1-(1-isobutylpiperidin-3-yl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(141);(R)-1-(1-(cyclopropylmethyl)piperidin-3-yl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(142);(R)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-(tetrahydro-2H-pyran-4-yl)piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(143);(R)-1-(1-ethylpiperidin-3-yl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(144);(R)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-1-(1-isopropylpiperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(145);(R)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-1-(1-(oxetan-3-yl)piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (146);(R)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-1-(1-methylpiperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(147);(R)-1-(1-(2-ethylbutyl)piperidin-3-yl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(148);(R)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-1-(1-((tetrahydro-2H-pyran-4-yl)methyl)piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(149);(R)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-1-(1-propylpiperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(150);(R)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-(2-ethylbutyl)piperidin-3-yl)-6-isopropyl-1,3-dihydro-2H-benzo[d]imidazol-2-one(151);(R)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-1-(1-neopentylpiperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(152);(R)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-neopentylpiperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(153);6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-methylpiperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(154);6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-propylpiperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(155);1-(1-cyclobutylpiperidin-4-yl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(156);6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-(oxetan-3-yl)piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (157);6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-(tetrahydro-2H-pyran-4-yl)piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(158);6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-((tetrahydro-2H-pyran-4-yl)methyl)piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(159);6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-((tetrahydrofuran-3-yl)methyl)piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(160);1-(1-(cyclopropylmethyl)piperidin-4-yl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(161);6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-(tetrahydrofuran-3-yl)piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(162);6-isopropyl-1-(1-isopropylpiperidin-4-yl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(163);1-(1-isobutylpiperidin-4-yl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(164);1-(1-(2-ethylbutyl)piperidin-4-yl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(165);6-ethyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-((1s,4s)-4-((tetrahydro-2H-pyran-4-yl)amino)cyclohexyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(166);6-ethyl-1-((1s,4s)-4-(isopropylamino)cyclohexyl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(167);1-((1s,4s)-4-(dipropylamino)cyclohexyl)-6-ethyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(168);1-((1s,4s)-4-(diethylamino)cyclohexyl)-6-ethyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(169);6-ethyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-((1s,4s)-4-(oxetan-3-ylamino)cyclohexyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(170);(R)-6-ethyl-1-(1-ethylpiperidin-3-yl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(171);(R)-6-ethyl-1-(1-isopropylpiperidin-3-yl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(172);(R)-6-ethyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-(oxetan-3-yl)piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (173);(R)-6-ethyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-methylpiperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(174);(R)-6-ethyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-((tetrahydro-2H-pyran-4-yl)methyl)piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(175);1-((3R)-1-(sec-butyl)piperidin-3-yl)-6-ethyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(176);(R)-6-ethyl-1-(1-isobutylpiperidin-3-yl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(177);(R)-6-ethyl-1-(1-(2-ethylbutyl)piperidin-3-yl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(178);(R)-6-ethyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-propylpiperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(179);(R)-6-ethyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-neopentylpiperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(180);(R)-1-(1-(cyclobutylmethyl)piperidin-3-yl)-6-ethyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(181);(R)-1-(1-(cyclopropylmethyl)piperidin-3-yl)-6-ethyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(182);(R)-6-ethyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-(3,3,3-trifluoropropyl)piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(183);(R)-6-ethyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-(tetrahydro-2H-pyran-4-yl)piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(184);5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-((1s,4s)-4-(dimethylamino)cyclohexyl)-6-isopropyl-1,3-dihydro-2H-benzo[d]imidazol-2-one (185);5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-1-((1s,4s)-4-(isopropylamino)cyclohexyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(186);5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-1-((1s,4s)-4-((tetrahydro-2H-pyran-4-yl)amino)cyclohexyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(187);5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-1-((1s,4s)-4-(oxetan-3-ylamino)cyclohexyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(188);5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-((1s,4s)-4-(ethylamino)cyclohexyl)-6-isopropyl-1,3-dihydro-2H-benzo[d]imidazol-2-one (189);5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-1-((1s,4s)-4-(neopentylamino)cyclohexyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(190);1-((1s,4s)-4-(dimethylamino)cyclohexyl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(191);6-isopropyl-1-((1s,4s)-4-(isopropylamino)cyclohexyl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(192);6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-((1s,4s)-4-((tetrahydro-2H-pyran-4-yl)amino)cyclohexyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(193);1-((1s,4s)-4-(2-ethylbutyl)amino)cyclohexyl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(194);6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-((1s,4s)-4-(propylamino)cyclohexyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(195);6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-((1s,4s)-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)cyclohexyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(196);6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-((1s,4s)-4-(neopentylamino)cyclohexyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(197);5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-((1s,4s)-4-((2-ethylbutyl)amino)cyclohexyl)-6-isopropyl-1,3-dihydro-2H-benzo[d]imidazol-2-one (198);5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-((1s,4s)-4-(dipropylamino)cyclohexyl)-6-isopropyl-1,3-dihydro-2H-benzo[d]imidazol-2-one (199);5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-1-((1s,4s)-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)cyclohexyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(200);6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-((1r,4s)-4-(oxetan-3-ylamino)cyclohexyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(201);1-((1r,4r)-4-(dimethylamino)cyclohexyl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(202);6-isopropyl-1-((1r,4s)-4-(isopropylamino)cyclohexyl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(203);1-((1r,4s)-4-(isobutylamino)cyclohexyl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(204);1-((1r,4r)-4-(thisobutylamino)cyclohexyl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(205);1-((1r,4r)-4-(bis(cyclopropylmethyl)amino)cyclohexyl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(206);6-isopropyl-1-((1r,4s)-4-((1-isopropylpiperidin-4-yl)amino)cyclohexyl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(207);(R)-1-(1-(3,3-dimethylbutyl)piperidin-3-yl)-6-ethyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(208);(R)-1-(1-(cyclopentylmethyl)piperidin-3-yl)-6-ethyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(209);(R)-1-(1-(3,3-dimethylbutyl)piperidin-3-yl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(210);(R)-1-(1-(cyclopentylmethyl)piperidin-3-yl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(211);6-ethyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-((3R)-1-(tetrahydrofuran-3-yl)piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(212);6-ethyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-((3R)-1-(tetrahydrofuran-3-yl)piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(213);6-ethyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-((3R)-1-(tetrahydro-2H-pyran-3-yl)piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(214-215);6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-((3R)-1-(tetrahydrofuran-3-yl)piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(216-217);6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-((3R)-1-(tetrahydro-2H-pyran-3-yl)piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(218-219);(S)-2-(3-(6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidin-1-yl)acetamide(220);(S)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-(2-methoxyethyl)piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(221);(S)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-(2-(methylsulfonyl)ethyl)piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(222);6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-(2-methoxyethyl)piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (223);6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-(2-(methylsulfonyl)ethyl)piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(224);(R)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-(2-methoxyethyl)piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(225);(R)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-(2-methoxyethyl)piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(226);(R)-6-ethyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(1-(2-methoxyethyl)piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (227);(R)-1-(1-(dimethylglycyl)piperidin-3-yl)-6-ethyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(228);1-(4-(4,4-difluoropiperidin-1-yl)cyclohexyl)-6-isopropyl-5-(8-methoxy-7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(229-230);6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(4-(pyrrolidin-1-yl)cyclohexyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (231);6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(4-(pyrrolidin-1-yl)cyclohexyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (232);6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(4-(3-oxopiperazin-1-yl)cyclohexyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(233-234);1-(4-(7-oxa-2-azaspiro[3.5]nonan-2-yl)cyclohexyl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(235-236);6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(4-(3-methoxyazetidin-1-yl)cyclohexyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(237-238);1-(4-(2-oxa-7-azaspiro[3.5]nonan-7-yl)cyclohexyl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(239-240);1-(4-(3-hydroxy-3-(trifluoromethyl)azetidin-1-yl)cyclohexyl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(241-242);6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(4-(3-oxopiperazin-1-yl)cyclohexyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(243);1-(4-(2,2-dioxido-2-thia-6-azaspiro[3.3]heptan-6-yl)cyclohexyl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(244-245);1-(4-(4,4-difluoropiperidin-1-yl)cyclohexyl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(246-247);6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(4-(methyl(3,3,3-trifluoropropyl)amino)cyclohexyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(248-249);6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(4-thiomorpholinocyclohexyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(250-251);1-(4-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)cyclohexyl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(252-253);1-(4-(2-oxa-6-azaspiro[3.3]heptan-6-yl)cyclohexyl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(254);6-isopropyl-5-(8-methoxy-7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(4-((2-methoxyethyl)amino)cyclohexyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(257-258);6-isopropyl-5-(8-methoxy-7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(4-((1-(methylsulfonyl)cyclopropyl)methyl)amino)cyclohexyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(259-260);1-(4-(1,4-oxazepan-4-yl)cyclohexyl)-6-isopropyl-5-(8-methoxy-7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(261-262);1-(4-(3-fluoroazetidin-1-yl)cyclohexyl)-6-isopropyl-5-(8-methoxy-7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(263-264);6-isopropyl-5-(8-methoxy-7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(4-(3-methoxyazetidin-1-yl)cyclohexyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(265-266);1-(4-(2-oxa-7-azaspiro[3.5]nonan-7-yl)cyclohexyl)-6-isopropyl-5-(8-methoxy-7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(267-268);1-(4-(2-oxa-6-azaspiro[3.3]heptan-6-yl)cyclohexyl)-6-isopropyl-5-(8-methoxy-7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(269-270);1-(4-(1,4-oxazepan-4-yl)cyclohexyl)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-1,3-dihydro-2H-benzo[d]imidazol-2-one(271-272);5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(4-(3-fluoropiperidin-1-yl)cyclohexyl)-6-isopropyl-1,3-dihydro-2H-benzo[d]imidazol-2-one (273-274);1-(4-(4,4-difluoropiperidin-1-yl)cyclohexyl)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-1,3-dihydro-2H-benzo[d]imidazol-2-one(275-276);5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-1-(4-(3-methoxyazetidin-1-yl)cyclohexyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(277-278);5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(4-(3-fluoroazetidin-1-yl)cyclohexyl)-6-isopropyl-1,3-dihydro-2H-benzo[d]imidazol-2-one (279-280);1-(4-(2-oxa-6-azaspiro[3.3]heptan-6-yl)cyclohexyl)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-1,3-dihydro-2H-benzo[d]imidazol-2-one(281);1-(4-(2-oxa-7-azaspiro[3.5]nonan-7-yl)cyclohexyl)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-1,3-dihydro-2H-benzo[d]imidazol-2-one(282-283);6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(4-(3-methoxypyrrolidin-1-yl)cyclohexyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(284-285);(S)-1-(4-(3-fluoropyrrolidin-1-yl)cyclohexyl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(286-287);6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(4-(3-(methylsulfonyl)pyrrolidin-1-yl)cyclohexyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(288-289);(R)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(4-(3-(methoxymethyl)pyrrolidin-1-yl)cyclohexyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(290-291);1-(4-((3S,4R)-3,4-difluoropyrrolidin-1-yl)cyclohexyl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(292-293);1-(4-(3,3-difluoropyrrolidin-1-yl)cyclohexyl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(294-295);1-(4-(3,3-difluoroazetidin-1-yl)cyclohexyl)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(296);1-(4-(2-oxa-6-azaspiro[3.3]heptan-6-yl)cyclohexyl)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-1,3-dihydro-2H-benzo[d]imidazol-2-one(297);5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1-(piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(1E);6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(1EA);5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(1EB);6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(1EC);(R)-6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(1ED);1-((1r,4s)-4-aminocyclohexyl)-6-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(1EF);-((1s,4s)-4-aminocyclohexyl)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1,3-dihydro-2H-benzo[d]imidazol-2-one(1EG);(R)-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-methyl-1-(piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(1EH);5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(1EG);7-methyl-5-(8-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(106F);(S)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(110F);(R)-6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(119F);6-isopropyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(119FA);(R)-6-ethyl-5-(8-methoxy-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-1-(piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(119FB); or(R)-5-(7,8-dimethyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)-6-isopropyl-1-(piperidin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one(119FC).
 16. A method of treating an autoimmune disease or a chronicinflammatory disease, comprising administering to a mammalian patent acompound according to claim 1 or a pharmaceutically acceptable saltthereof, wherein said autoimmune disease or chronic inflammatory diseaseis selected from systemic lupus erythematosus (SLE), rheumatoidarthritis, multiple sclerosis (MS), and Sjögren's syndrome.